Rapid Onset of Renal Sympathetic Nerve Activation in Rabbits Fed a High-Fat Diet
Abstract
Hypertension and elevated sympathetic drive result from consumption of a high-calorie diet and deposition of abdominal fat, but the etiology and temporal characteristics are unknown. Rabbits instrumented for telemetric recording of arterial pressure and renal sympathetic nerve activity (RSNA) were fed a high-fat diet for 3 weeks then control diet for 1 week or control diet for 4 weeks. Baroreflexes and responses to air-jet stress and hypoxia were determined weekly. After 1 week of high-fat diet, caloric intake increased by 62%, accompanied by elevated body weight, blood glucose, plasma insulin, and leptin (8%, 14%, 134%, and 252%, respectively). Mean arterial pressure, heart rate, and RSNA also increased after 1 week (6%, 11%, and 57%, respectively). Whereas mean arterial pressure and body weight continued to rise over 3 weeks of high-fat diet, heart rate and RSNA did not change further. The RSNA baroreflex was attenuated from the first week of the diet. Excitatory responses to air-jet stress diminished over 3 weeks of high-fat diet, but responses to hypoxia were invariant. Resumption of a normal diet returned glucose, insulin, leptin, and heart rate to control levels, but body weight, mean arterial pressure, and RSNA remained elevated. In conclusion, elevated sympathetic drive and impaired baroreflex function, which occur within 1 week of consumption of a high-fat, high-calorie diet, appear integral to the rapid development of obesity-related hypertension. Increased plasma leptin and insulin may contribute to the initiation of hypertension but are not required for maintenance of mean arterial pressure, which likely lies in alterations in the response of neurons in the hypothalamus.
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Written from the paper’s full text.
TL;DR
In conscious rabbits, a high-fat, high-calorie diet increased renal sympathetic nerve activity (RSNA), heart rate, and mean arterial pressure within 1 week, alongside rapid rises in glucose, insulin, and leptin. Withdrawal of the diet normalized glucose, insulin, leptin, and heart rate, but body weight, mean arterial pressure, and RSNA remained elevated.
Key findings
- After 1 week of high-fat diet, caloric intake rose by 62%, and body weight, blood glucose, plasma insulin, and leptin increased by 8%, 14%, 134%, and 252%, respectively; mean arterial pressure, heart rate, and RSNA increased by 6%, 11%, and 57%, respectively.
- Mean arterial pressure and body weight continued to rise over 3 weeks of high-fat diet, whereas heart rate and RSNA did not change further; the RSNA baroreflex was attenuated from week 1, with the lower plateau 92% higher and range 29% lower at week 3, and gain 48% lower at week 3.
- Excitatory responses to air-jet stress diminished over 3 weeks of high-fat diet (RSNA response −70% at week 3), but responses to hypoxia were invariant.
- After return to normal diet, glucose, insulin, leptin, and heart rate returned to control levels, but body weight, mean arterial pressure, and RSNA remained elevated; ganglion blockade produced a greater fall in mean arterial pressure in high-fat-diet rabbits (−23±2 mm Hg, n=5) than controls (−13±2 mm Hg, n=4; P group=0.014).
Methods
- Experiments used 33 male New Zealand white rabbits (body weight 2.6–3.3 kg) instrumented under isoflurane anesthesia with telemetric arterial pressure recording and renal nerve electrodes; after recovery, baseline mean arterial pressure, heart rate, and RSNA were measured.
- Rabbits were randomized to a normal-fat control diet (n=10) or high-fat diet (n=13) for 3 weeks, then the high-fat group returned to control diet for 1 week; diets were standard rabbit chow (4.2% fat, 2.63 kcal/g) or modified chow (13.3% fat, 3.34 kcal/g).
- Weekly measurements included responses to air-jet stress and hypoxia, RSNA and heart rate baroreflexes derived from phenylephrine and sodium nitroprusside infusions, blood glucose, plasma insulin and leptin, and at week 3 ganglion blockade with pentolinium; data were analyzed by split-plot repeated-measures ANOVA, one-way ANOVA, and Bonferroni/Greenhouse-Geisser corrections, with P<0.05 significant.
Limitations
- The paper states that RSNA signal decay after approximately 5 weeks of recording meant only 3 to 4 rabbits per group had viable RSNA at week 4.
- The paper does not include a dedicated limitations section; evident from the text, some measures used small subsets (caloric intake n=4–5 per group, plasma insulin n=5 per group, plasma leptin n=4 control and 8 high-fat-diet rabbits, RSNA n=8 control and 6 high-fat-diet rabbits through week 3).
- Evident from the text, the study used only male rabbits and an acute fat-feeding model, and it did not directly establish causality for leptin, insulin, or other proposed mechanisms maintaining elevated mean arterial pressure and RSNA after diet withdrawal.
Model-written summary. Check it against the paper before relying on it.
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- Findingown data
In rabbits fed a high-fat diet, caloric intake increased by 62% after 1 week compared with baseline.
“After 1 week of high-fat diet, caloric intake increased by 62%, accompanied by elevated body weight, blood glucose, plasma insulin, and leptin (8%, 14%, 134%, and 252%, respectively).”
- Also stated in: § Effect of the HFD Over 3 Weeks and Return to Normal Diet · plain
“During the first week of HFD, calorie intake increased by 62% from 299Ϯ4 kcal • d Ϫ1 but declined from then until week 3 when intake was 42% greater than baseline (PϽ0.001;nϭ5; Figure 1).”
Quote in the paperNot a substantial claim - Also stated in: § Effect of the HFD Over 3 Weeks and Return to Normal Diet · plain
- Findingown data
In control rabbits, MAP and HR responses to air-jet stress over 3 weeks were similar to those observed during the baseline experiment.
“In control rabbits (nϭ8), the MAP and HR responses to air-jet stress over 3 weeks were similar to those observed during the baseline experiment (Figure 2).”
Quote in the paperSubstantial claim - Findingown data
Control animals showed no change in RSNA over the course of the experimental schedule.
“Control animals showed no change in RSNA over the course of the experimental schedule (Figure 1).”
Quote in the paperSubstantial claim - Findingown data
Insulin sensitivity showed a large rebound (+265%) in the first week after return to a normal diet.
“Insulin sensitivity showed a large rebound in the first week after return to a normal diet (ϩ265%).”
Quote in the paperNot a substantial claim - Findingown data
In rabbits fed HFD, renal sympathetic nerve activity increased by 57% after 1 week.
“Mean arterial pressure, heart rate, and RSNA also increased after 1 week (6%, 11%, and 57%, respectively).”
Quote in the paperSubstantial claim
- Findingown data
Three rabbits previously on the HFD with working electrodes demonstrated maintenance of high RSNA one week after return to a normal diet.
“Interestingly, the 3 rabbits previously on the HFD, which had working electrodes 1 week after return to a normal diet, demonstrated maintenance of the high RSNA.”
Quote in the paperNot a substantial claim - Findingown data
The nasopharyngeal response used to normalize RSNA was not altered by time on the HFD.
“The nasopharyngeal response that was used to normalize RSNA was not altered by time on the HFD (P groupϫdiet ϭ0.58).”
Quote in the paperSubstantial claim - Findingown data
After onset of HFD, MAP responses to air jet were reduced by 21% (weeks 1-2) compared with baseline.
“By contrast, after the onset of the HFD (nϭ11), the MAP responses to air jet were reduced by 21% (weeks 1-2; PϽ0.05) and the tachycardia reduced by 26% to 48% (weeks 2-3) compared with baseline (PϽ0.01; Figure 2).”
Quote in the paperSubstantial claim - Findingown data
Cardiovascular responses to air-jet stress were invariant between HFD and control animals.
“Our finding of invariant cardiovascular responses to air-jet stress between HFD and control animals”
Quote in the paperSubstantial claim - Findingown data
Normalization of caloric intake results in partial reversal of blood pressure even when body weight remains high.
“Normalization of caloric intake results in partial reversal of blood pressure even when body weight remains high”
Quote in the paperSubstantial claim - Findingown data
After onset of HFD, tachycardia response to air jet was reduced by 26% to 48% (weeks 2-3) compared with baseline.
“By contrast, after the onset of the HFD (nϭ11), the MAP responses to air jet were reduced by 21% (weeks 1-2; PϽ0.05) and the tachycardia reduced by 26% to 48% (weeks 2-3) compared with baseline (PϽ0.01; Figure 2).”
Quote in the paperNot a substantial claim - Findingown data
After 3 weeks HFD, fat mass was markedly greater than at 1 week.
“After 3 weeks HFD, fat mass (6.93 ± 0.98%) was markedly greater than at 1 week (P < 0.05).”
Quote in the paperNot a substantial claim - Findingown data
The reduction in air-jet sympathoexcitation became progressively greater in the HFD group over 3 weeks (-70% at week 3).
“However the reduction became progressively greater in the HFD group over the course of 3 weeks (Ϫ70% at week 3; P time Ͻ0.05), whereas we did not observe any further change in the response in the control group (Figure 2).”
Quote in the paperSubstantial claim - Findingown data
In control rabbits, no significant differences were observed between RSNA baroreflex curves at baseline and those constructed over the following 3 weeks.
“In control rabbits, we observed no significant differences between RSNA baroreflex curves at baseline and those constructed over the following 3 weeks (Figure 4 and Table S1, available in the online-only Data Supplement).”
Quote in the paperNot a substantial claim - Findingown data
HR baroreflexes measured in control rabbits, repeated 4 times at weekly intervals, were very similar to those produced at the baseline experiment.
“HR baroreflexes measured in control rabbits, which were repeated 4 times at weekly intervals, were also very similar to those produced at the baseline experiment (Figure 5 and Table S2).”
Quote in the paperNot a substantial claim - Findingown data
Rabbits fed a HFD for 3 weeks followed by 1 week normal diet showed a 2-3 fold greater weight of perirenal, mesenteric, testicular and bladder WAT compared with control rabbits in absolute terms or when expressed as % body weight.
“Rabbits fed a HFD for 3 weeks followed by 1 week normal diet showed a 2-3 fold greater weight of perirenal, mesenteric, testicular and bladder WAT compared with control rabbits in absolute terms or when expressed as % body weight (all P group < 0.001, Table S3).”
Quote in the paperNot a substantial claim - Findingreasoning
Withdrawal of the HFD resulted in rapid recovery of HR, which fell to baseline levels within 1 week.
“withdrawal of the HFD resulted in a rapid recovery of HR, which fell to baseline levels within 1 week.”
Quote in the paperSubstantial claim - Findingown data
The main effect of HFD on the HR baroreflex was to shift the curve in the direction of the MAP increase (8% increase in blood pressure at half the reflex range at week 3).
“By contrast, the main effect of the HFD on the HR baroreflex was to shift the curve in the direction of the MAP increase (8% increase in blood pressure at half the reflex range at week 3; PϽ0.001; Figure 5 and Table S2).”
Quote in the paperNot a substantial claim - Findingown data
The difference in left ventricular weight between HFD and control rabbits was abolished when weights were scaled to body weight.
“this difference was abolished when weights were scaled to body weight.”
Quote in the paperNot a substantial claim - Findingown data
Fat mass as percentage of body weight was greater in HFD fed rabbits than control rabbits after 1 week of diet.
“fat mass as a percentage of body weight was greater in HFD fed rabbits than control rabbits after 1 week of diet (4.50 ± 0.00% vs 2.55 ± 0.35%, respectively, P < 0.05).”
Quote in the paperNot a substantial claim - Findingown data
Consumption of HFD and then return to a normal diet did not significantly alter responses to hypoxia.
“Consumption of the HFD and then return to a normal diet did not significantly alter these responses (P group Ͼ0.05; Figure 3).”
Quote in the paperNot a substantial claim - Findingown data
In rabbits fed HFD, there was a marked progressive increase in the lower plateau of the RSNA baroreflex from week 1 until week 3, when the minimum RSNA was 92% higher than at baseline.
“In rabbits fed the HFD, there was a marked progressive increase in the lower plateau of the RSNA baroreflex, from week 1 until week 3, when the minimum RSNA was 92% higher than at baseline (PϽ0.001; Figure 4 and Table S1).”
Quote in the paperSubstantial claim - Findingown data
There was progressive diminution of blood pressure, HR, and RSNA responses to stress as the HFD progressed.
“we observed progressive diminution of blood pressure, HR, and RSNA responses to stress as the HFD diet progressed.”
Quote in the paperSubstantial claim - Findingown data
RSNA baroreflex gain was markedly reduced at weeks 2 and 3 (-48% at week 3).
“RSNA baroreflex gain, which depends on range, was also markedly reduced at weeks 2 and 3 (Ϫ48% at week 3; Pϭ0.003; Figure 4 and Table S1).”
Quote in the paperSubstantial claim - Findingown data
BAT weight in HFD rabbits was more than double that of control rabbits.
“BAT weight in HFD rabbits was also more than double that of control rabbits (P group < 0.01, Table 4).”
Quote in the paperNot a substantial claim - Findingown data
RSNA increases in conscious, unrestrained animals as they develop obesity-related hypertension.
“We have now shown that RSNA increases in conscious, unrestrained animals as they develop obesity-related hypertension”
Quote in the paperSubstantial claim - Findingown data
Lean body mass and bone mineral content were not altered by 1 or 3 weeks of HFD.
“Lean body mass and bone mineral content were not altered by 1 or 3 weeks of HFD.”
Quote in the paperNot a substantial claim - Findingown data
In the first and subsequent weeks of HFD intake, there was a reduction in RSNA baroreflex gain and range brought about by an elevation of the lower plateau without any change in the upper plateau.
“In the first and subsequent weeks of HFD intake, there was a reduction in the RSNA baroreflex gain and range brought about by an elevation of the lower plateau without any change in upper plateau.”
Quote in the paperSubstantial claim - Findingown data
Lean muscle mass as percentage of body weight was reduced in 3 week HFD fed rabbits compared to controls.
“Lean muscle mass as percentage of body weight was reduced in 3 week HFD fed rabbits compared to controls (P < 0.01).”
Quote in the paperNot a substantial claim - Findingown data
There was little change in the upper plateau of the RSNA baroreflex over the 3 weeks of HFD.
“This resulted in an attenuation of the baroreflex range (29% at week 3; PϽ0.001), because there was little change in the upper plateau over this time period (Figure 4 and Table S1).”
Quote in the paperSubstantial claim - Findingreasoning
HFD resulted in attenuation of the RSNA baroreflex range (29% at week 3).
“This resulted in an attenuation of the baroreflex range (29% at week 3; PϽ0.001), because there was little change in the upper plateau over this time period (Figure 4 and Table S1).”
Quote in the paperSubstantial claim - Findingown data
In control rabbits and in rabbits fed HFD, no change in responses to hypoxia was observed over the following 3 weeks.
“In control rabbits and in rabbits fed the HFD, we observed no change in the responses to hypoxia over the following 3 weeks (Figure 3).”
Quote in the paperNot a substantial claim - Findingown data
Ganglion blockade in rabbits fed HFD for 3 weeks produced a fall in MAP (-23±2 mm Hg), which was almost double that observed in control rabbits (-13±2 mm Hg).
“Ganglion blockade in rabbits fed the HFD for 3 weeks produced a fall in MAP (Ϫ23Ϯ2 mm Hg; nϭ5), which was almost double that observed in control rabbits (Ϫ13Ϯ2 mm Hg; nϭ4; P group ϭ0.014).”
Quote in the paperSubstantial claim - Findingown data
After return to control diet, there was no significant difference between RSNA responses to air-jet in the two groups.
“After the return to control diet, there was no significant difference between RSNA responses in the 2 groups (nϭ3-4; Figure 2).”
Quote in the paperSubstantial claim - Findingown data
Sympathoexcitation in response to air-jet stress was reduced in both control and HFD rabbits compared with baseline.
“Sympathoexcitation in response to air-jet stress was reduced in both control and HFD rabbits compared with the baseline response (Figure 2).”
Quote in the paperNot a substantial claim - Findingown data
RSNA remains elevated when the high-fat diet is withdrawn.
“Even when the high-fat diet is withdrawn, RSNA remains high.”
Quote in the paperSubstantial claim - Findingown data
Blood pressure remains elevated when the high-fat diet is withdrawn.
“Blood pressure and RSNA remain elevated when the diet is withdrawn”
Quote in the paperSubstantial claim - Interpretationreasoning
Sympathetic nervous system activation in obesity occurs to maintain energy homeostasis.
“sympathetic nervous system activation in obesity occurs to maintain energy homeostasis”
Quote in the paperSubstantial claim - Interpretationown data
Elevated RSNA occurs very early in the development of obesity-related hypertension.
“These data show that elevated RSNA occurs very early in the development of obesity-related hypertension, and ganglionic blockade data suggest that much of the observed hypertension is attributable to elevated sympathetic activity.”
Quote in the paperSubstantial claim - Premisecitation
In humans with significant visceral adiposity, obesity hypertension is characterized by a reduction in baroreceptor inhibition.
“The hypertension in obesity is characterized by a reduction in baroreceptor inhibition in humans 31 when there is significant visceral adiposity”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [31] source
Not checked in the free run.
- Interpretationown data
Baroreflex control of RSNA did not simply reset toward the higher level of BP.
“the baroreflex control of RSNA did not simply reset toward the higher level of BP”
Quote in the paperSubstantial claim - Interpretationown data
The development of hypertension in this model is attributed almost entirely to elevated whole body sympathetic tone.
“The ganglionic blockade experiments offer clear evidence that the development of hypertension is attributed almost entirely to elevated whole body sympathetic tone, and although there is variation in sympathetic”
Quote in the paperSubstantial claim - Interpretationown data
The pattern of increase in plasma insulin and leptin mirrors that of HR, MAP, and RSNA.
“This pattern of increase mirrors that of HR, MAP, and RSNA, suggesting a possible role for insulin, as well as leptin, in the development of obesity-related hypertension.”
Quote in the paperSubstantial claim - Interpretationreasoning
The fall in hemodynamic factors after HFD withdrawal is not dependent on a fall in body weight or low body fat.
“this fall in hemodynamic factors is not dependent on a fall in body weight or low body fat”
Quote in the paperSubstantial claim - Interpretationown data
RSNA increases rapidly in the first week of fat feeding, well before the onset of frank obesity.
“Our present data now indicate that RSNA increases rapidly in the first week of fat feeding, well before the onset of frank obesity.”
Quote in the paperSubstantial claim - Interpretationreasoning
Elevated hemodynamics occur under conditions of caloric load.
“These observations support the hypothesis that elevated hemodynamics occur under conditions of caloric load.”
Quote in the paperSubstantial claim- Rests on an assumption: The observed effects of high-fat diet in rabbits are attributable to caloric load rather than high fat content per se.
- Interpretationown data
Much of the observed hypertension in HFD rabbits is attributable to elevated sympathetic activity.
“These data show that elevated RSNA occurs very early in the development of obesity-related hypertension, and ganglionic blockade data suggest that much of the observed hypertension is attributable to elevated sympathetic activity.”
Quote in the paperSubstantial claim - Interpretationown data
Obesity-related hypertension is neurogenic.
“provides further evidence that obesity-related hypertension is neurogenic.”
Quote in the paperSubstantial claim - Interpretationreasoning
The 20% increase in RSNA would contribute significantly to the MAP elevation.
“it is likely that the 20% increase in RSNA would contribute significantly to this MAP elevation.”
Quote in the paperSubstantial claim - Interpretationown data
Early in the development of obesity-related hypertension, there is no potentiation of stress pathways.
“suggests that, early in the development of obesity-related hypertension, there is no potentiation of stress pathways.”
Quote in the paperSubstantial claim- Rests on an assumption: The air-jet stress and hypoxia protocols adequately model emotional stress and chemoreflex activation in the context of obesity-related hypertension.
- Rests on an assumption: The first 3 weeks of HFD in rabbits correspond to the early phase of human obesity-related hypertension.
- Interpretationown data
Altered chemoreflex activity is not an instigating factor for obesity-related hypertension.
“Our data indicate that altered chemoreflex activity is not an instigating factor for obesity-related hypertension.”
Quote in the paperSubstantial claim - Interpretationown data
The chemoreflex is not changed in the early phase of obesity-related hypertension.
“indicating that the chemoreflex is not changed in the early phase of obesity-related hypertension.”
Quote in the paperSubstantial claim- Rests on an assumption: The air-jet stress and hypoxia protocols adequately model emotional stress and chemoreflex activation in the context of obesity-related hypertension.
- Rests on an assumption: The first 3 weeks of HFD in rabbits correspond to the early phase of human obesity-related hypertension.
- Interpretationown data
Elevated sympathetic drive appears important for obesity-related hypertension.
“Elevated sympathetic drive appears to be important for obesityrelated hypertension”
Quote in the paperSubstantial claim - Interpretationreasoning
Increased plasma leptin and insulin may contribute to the initiation of hypertension.
“although increased plasma leptin and insulin may contribute to the initiation of hypertension”
Quote in the paperSubstantial claim - Interpretationreasoning
Increased plasma leptin and insulin are not required for the maintenance of hypertension.
“they are not required for its maintenance.”
Quote in the paperSubstantial claim
- May combine two claims. 34
- Classified as probably not a substantial claim. 13
May combine two claims.
Findingown dataAfter return to a normal diet, body weight and mean arterial pressure in rabbits previously fed HFD remained elevated compared with control rabbits, although MAP was 4% lower than the peak response.
“However, body weight and MAP in rabbits previously fed the HFD remained elevated compared with control rabbits (P groups Ͻ0.001), although MAP was 4% lower than the peak response (Pϭ0.002for week 3 versus recovery; Figure 1).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn rabbits fed HFD, insulin sensitivity estimated by the glucose/insulin ratio declined rapidly and was 47% lower than baseline during weeks 1 to 3.
“Insulin sensitivity, estimated by the glucose/insulin ratio, showed a rapid decline with HFD consumption and was 47% lower than baseline during weeks 1 to 3 of the HFD (P groupϫdiet ϭ0.042).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataOne week after resuming a normal diet, calorie intake fell to a level similar to control rabbits, accompanied by falls in blood glucose, plasma insulin, plasma leptin, and heart rate.
“One week after resuming a normal diet, calorie intake had fallen to a level similar to that of control rabbits, accompanied by falls in blood glucose, plasma insulin, and plasma leptin concentrations, as well as HR (Figure 1).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn rabbits fed HFD, plasma leptin increased by 252% at week 1 and remained elevated throughout the HFD.
“(ϩ252%; PϽ0.001) and remained elevated throughout the HFD, whereas plasma leptin concentration in control rabbits did not change over the same period (Figure 1).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn rabbits fed HFD, renal sympathetic nerve activity increased by 3.1±0.7 normalized units at week 1 and was maintained throughout the treatment period.
“There was a marked increase in RSNA at week 1 of the HFD (ϩ3.1Ϯ0.7 normalized units; PϽ0.001), which was maintained throughout the treatment period (Figure 1).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn rabbits fed HFD, heart rate increased by 11% at week 1 and remained at a similar level during the following 2 weeks.
“HR, by contrast, increased by 11% at week 1 (PϽ0.001)and remained at a similar level during the following 2 weeks (Figure 1).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn control rabbits, mean arterial pressure, heart rate, and renal sympathetic nerve activity did not change significantly over the 3-week treatment period.
“By contrast, MAP, HR, and RSNA in rabbits fed a control diet did not change significantly over the 3-week treatment period (P time Ͼ0.05Ͻ0.001; Figure 1).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn rabbits fed HFD, plasma insulin increased by 134% during the first week and remained elevated for the next 2 weeks.
“Blood glucose and plasma insulin concentrations were initially similar in the 2 groups (Table) but increased significantly during the first week of the HFD (ϩ14% and ϩ134%, respectively; PϽ0.001) and remained elevated for the next 2 weeks (Figure 1).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn rabbits fed HFD, body weight increased by 260±35 g during the first week and by 504±43 g at week 3, compared with control rabbits gaining 80±26 g by week 3.
“Rabbits fed the HFD (nϭ13) gained 260Ϯ35 g during the first week and continued to gain weight over the next 2 weeks (504Ϯ43 g at week 3) compared with control rabbits, which had gained 80Ϯ26 g by week 3 (nϭ10; P group Ͻ0.001; Figure 1).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn rabbits fed HFD, blood glucose increased by 14% during the first week and remained elevated for the next 2 weeks.
“Blood glucose and plasma insulin concentrations were initially similar in the 2 groups (Table) but increased significantly during the first week of the HFD (ϩ14% and ϩ134%, respectively; PϽ0.001) and remained elevated for the next 2 weeks (Figure 1).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataInitial responses to air-jet stimulus were similar in control and HFD groups and consisted of a rapid increase in MAP (+18±1 mm Hg), tachycardia (+29±2 beats/min), and sympathoexcitation (+3.5±0.4 normalized units).
“Initial responses to the air-jet stimulus were similar in the 2 groups and consisted of a rapid increase in MAP (ϩ18Ϯ1 mm Hg), tachycardia (ϩ29Ϯ2 beats • min Ϫ1 ) and sympathoexcitation (ϩ3.5Ϯ0.4 normalized units).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn rabbits fed HFD, mean arterial pressure increased by 6% during the first week and by 12% at week 3.
“MAP increased by 6% during the first week of HFD (PϽ0.001), but by week 3 that increase had doubled to 12% (Figure 1).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataBy week 3, the HR baroreflex upper plateau and reflex range had recovered and were greater than baseline (6% to 8%), and there was restoration of baroreflex gain toward the baseline value.
“However, by week 3, the HR baroreflex upper plateau and reflex range had recovered and were greater than baseline (6% to 8%; PϽ0.05), and there was restoration of baroreflex gain toward the baseline value (Pϭ0.2; Figure 5 and Table S2).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataScaled weight of the liver was significantly less in HFD rabbits than controls.
“Interestingly, scaled weight of the liver was significantly less in HFD rabbits than controls (HFD 2.7 % vs control 3.1 %, P group = 0.01).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataAfter 1 week of control diet in rabbits previously fed HFD, both MAP and HR responses to air-jet stress were restored to baseline levels and were similar to responses in control rabbits.
“After 1 week of control diet in rabbits previously fed the HFD, both the MAP and HR responses to air-jet stress were restored to baseline levels and were similar to responses in control rabbits (Figure 2).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataHR baroreflex curves constructed 1 week after rabbits on the HFD were returned to a normal diet were still enhanced, most notably baroreflex gain, which was 33% greater than at week 3 but not different from baseline.
“HR baroreflex curves constructed 1 week after rabbits on the HFD were returned to a normal diet were still enhanced, most notably baroreflex gain, which was 33% greater than at week 3 (PϽ0.001)but not different from baseline (Table S2).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataRSNA and HR baseline baroreflex curves were sigmoidal, with resting values lying close to the lower plateau.
“RSNA and HR baseline baroreflex curves were sigmoidal, with resting values lying close to the lower plateau.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe gain of the HR baroreflex was reduced during HFD consumption but normalized on withdrawal of the HFD.
“The gain of the HR baroreflex was also reduced during HFD consumption but normalized on withdrawal of the HFD.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataShort-term HFD consumption results in alterations to the HR and RSNA baroreflexes.
“Our data indicate that short-term HFD consumption results in alterations to the HR and RSNA baroreflexes.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataLeft ventricular weight was 11% greater in rabbits previously fed HFD than controls.
“Although left ventricular weight was 11 % greater in rabbits previously fed a HFD than controls (HFD 4.6 g vs control 4.2 g, P group = 0.01)”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataWeights of kidneys and adrenal glands were similar in both treatment groups.
“The weights of kidneys and adrenal glands were similar in both treatment groups.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingnone givenRSNA, HR, MAP, plasma insulin, and plasma leptin increase in the first week of a high-fat, high-calorie diet in conscious rabbits.
“RSNA, HR, MAP, plasma insulin, and plasma leptin increase in the first week of a high-fat, high-calorie diet in conscious rabbits.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataOver the 3 weeks of fat feeding, rabbits developed an increase in adipose tissue mass distributed across perirenal, mesenteric, testicular, bladder white adipose tissue depots and brown adipose tissue depots, which was maintained after 1 week of normal diet.
“Over the 3 weeks of fat feeding, rabbits developed an increase in adipose tissue mass distributed across perirenal, mesenteric, testicular, bladder white adipose tissue depots (P group Ͻ0.001), and brown adipose tissue depots (P group Ͻ0.01), which was maintained after 1 week of normal diet.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThere was initially an attenuation of the HR baroreflex at week 1, with an elevation of the lower plateau and reductions in reflex range and gain compared with baseline.
“There was initially an attenuation of the curve at week 1, with an elevation of the lower plateau and reductions in reflex range and gain compared with baseline (Figure 5 and Table S2).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe MAP, HR, or RSNA response to hypoxia was not different from controls in HFD rabbits.
“the MAP, HR, or RSNA response to hypoxia was not different from controls”
Quote in the paperSubstantial claimMay combine two claims.
Findingnone givenRabbits consuming the HFD ingested approximately 200 kcal per day more than controls, representing a 40% to 60% increase above basal energy intake.
“Rabbits consuming the HFD ingested Ϸ200 kcal per day more than controls, which represents a 40% to 60% increase above basal energy intake.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataAt baseline, rabbits in control and HFD groups showed characteristic pressor (+4.5±0.4 mm Hg), tachycardic (+18±1 beats/min), and sympathoexcitatory (+2.5±0.3 normalized units) responses to hypoxia.
“At the baseline experiment, rabbits in control (nϭ10) and HFD (nϭ13) groups showed characteristic pressor (ϩ4.5Ϯ0.4 mm Hg), tachycardic (ϩ18Ϯ1 beats • min Ϫ1 ), and sympathoexcitatory (ϩ2.5Ϯ0.3 normalized units) responses to hypoxia.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataInsulin and leptin return to normal when the high-fat diet is withdrawn.
“but insulin and leptin return to normal.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataThe reduction in stress response is not habituation for MAP or HR, because the response to air-jet stress returned to baseline levels on withdrawal of the HFD.
“This reduction in response is not habituation for MAP or HR at least, because the response to air-jet stress returned to baseline levels on withdrawal of the HFD.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationWeight loss is associated with reactivation of the baroreflex.
“weight loss is associated with reactivation of the baroreflex, 14”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [14] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIncreased cardiovascular responses to emotional stress are pivotal in the development of hypertension.
“A number of studies implicate increased cardiovascular responses to emotional stress as being pivotal in the development of hypertension.28,29”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThere is a decrease in baroreceptor sensitivity in patients with long-term obstructive sleep apnea.
“There is also a decrease in baroreceptor sensitivity in patients with long-term obstructive sleep apnea.38”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [38] source
Not checked in the free run.
May combine two claims.
Interpretationown dataSympathetic drive is increased rapidly on consumption of a high-calorie diet and is central to obesity-related hypertension.
“supporting the hypothesis that sympathetic drive is increased rapidly on consumption of a high calorie diet and is central to obesity-related hypertension.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataThe relationship among insulin, leptin, and MAP appears more complex than previously reported because the rising trend of MAP follows that of insulin and leptin during the onset of obesity but does not appear to hold after withdrawal of HFD.
“The relationship among insulin, leptin, and MAP appears more complex than we have reported previously, 9 because the rising trend of MAP follows that of insulin and leptin during the onset of obesity but does not appear to hold after the withdrawal of HFD, where plasma leptin and insulin concentrations fall rapidly but MAP and RSNA remain high.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [9] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationRepeated episodes of hypoxia, either from obstructive sleep apnea or experimental induction, result in elevation of blood pressure and altered metabolic function.
“Repeated episodes of hypoxia, either occurring as a result of obstructive sleep apnea 35 or because of experimental induction, both result in elevation of blood pressure 36 and altered metabolic function.37”
Quote in the paperNot a substantial claim0 of 3 sources checkedMay combine two claims.
InterpretationreasoningA feed-forward sympathoexcitatory mechanism involving activation of nonbaroreceptor-dependent RSNA may be responsible for the increase in RSNA rather than an impaired baroreflex.
“it appears that a feed-forward sympathoexcitatory mechanism involving activation of nonbaroreceptor-dependent RSNA may be responsible for the increase in RSNA rather than an impaired baroreflex.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningThis phase of obesity-related hypertension is associated with alterations in the baroreflex, but stress and chemoreflex pathways do not appear to be involved.
“This phase of obesity-related hypertension is associated with alterations in the baroreflex, but stress and chemoreflex pathways do not appear to be involved.”
Quote in the paperSubstantial claim- Rests on an assumption: The first 3 weeks of HFD in rabbits correspond to the early phase of human obesity-related hypertension.
May combine two claims.
InterpretationreasoningThe fall in hemodynamic factors after HFD withdrawal may be related to plasma insulin and glucose concentrations, which return to baseline within 1 week of recovery.
“may be more likely related to plasma insulin and glucose concentrations, which also return to baseline within 1 week of recovery from the HFD.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe dorsomedial hypothalamus is pivotal in the transduction of the stress response.
“We have shown previously that the dorsomedial hypothalamus is pivotal in the transduction of the stress response.30”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [30] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationObese humans demonstrate an exacerbated cardiovascular and sympathetic response to mental and cold pressor stressors.
“It is also reported that obese humans demonstrate an exacerbated cardiovascular and sympathetic response to mental and cold pressor stressors.13”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [13] source
Not checked in the free run.
Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).
InterpretationreasoningObesity-related hypertension is a negative adverse effect.
“obesity-related hypertension is a negative adverse effect.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationElevation in subcutaneous adiposity does not alter the baroreflex.
“elevation in subcutaneous adiposity does not alter the baroreflex.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [31] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationActivation of the baroreflex by exogenous electric stimulation of carotid sinus baroreceptors in obese hypertensive dogs results in a reduction in MAP, HR, and plasma norepinephrine concentrations.
“activation of the baroreflex by exogenous electric stimulation of the carotid sinus baroreceptors in obese hypertensive dogs results in a reduction in MAP, HR, and plasma norepinephrine concentrations.32”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [32] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.
Interpretationnone givenDuring the weight gain phase, MAP and RSNA rise rapidly, but even after successfully reducing caloric intake, these individuals may retain elevated RSNA and MAP.
“During the weight gain phase, MAP and RSNA rise rapidly, but even after successfully reducing caloric intake, these individuals may retain elevated RSNA and MAP.”
Quote in the paperNot a substantial claim- Rests on an assumption: Findings in rabbits can be generalized to humans in weight gain and acute dieting cycles.
May combine two claims.
Interpretationown dataElevated sympathetic drive and impaired baroreflex function appear integral to the rapid development of obesity-related hypertension.
“Elevated sympathetic drive and impaired baroreflex function appear integral to the rapid development of obesity-related hypertension.”
Quote in the paperSubstantial claim
The paper relies on this without support.
The observed effects of high-fat diet in rabbits are attributable to caloric load rather than high fat content per se.
“RSNA, HR, MAP, plasma insulin, and plasma leptin increase in the first week of a high-fat, high-calorie diet in conscious rabbits.”
The paper relies on this without support.
Findings in rabbits can be generalized to humans in weight gain and acute dieting cycles.
“this has implications for cardiovascular health in people who are constantly in a cycle of weight gain and acute dieting to reduce body weight.”
The paper relies on this without support.
The air-jet stress and hypoxia protocols adequately model emotional stress and chemoreflex activation in the context of obesity-related hypertension.
“Our finding of invariant cardiovascular responses to air-jet stress between HFD and control animals”
“the MAP, HR, or RSNA response to hypoxia was not different from controls”
The paper relies on this without support.
The first 3 weeks of HFD in rabbits correspond to the early phase of human obesity-related hypertension.
“early in the development of obesity-related hypertension”
“early phase of obesity-related hypertension”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In rabbits, renal sympathetic nerve activity increases within a few days of starting a high-fat diet.
“In rabbits, RSNA increases within a few days of starting an HFD155.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [155]
Similar results of impaired baroreflexes were found in rabbits fed a high-fat diet.
“Similar results were found in rabbits fed an HFD155.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [155]
Cardiac and renal sympathetic nerve activity baroreflex sensitivity is depressed after rapid weight gain and in the setting of long-standing obesity in experimental animals and humans.
“Studies in experimental animals and humans indicate that cardiac and RSNA baroreflex sensitivity is depressed after rapid weight gain and in the setting of long-standing obesity37,155,179.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [155]
The metabolic, endocrine, cardiovascular, and renal changes caused by dietary-induced obesity in dogs and rabbits closely mimic the changes observed in obese humans.
“The metabolic, endocrine, cardiovascular, and renal changes caused by dietary-induced obesity in these experimental animals closely mimic the changes observed in obese humans5,13–16 (Table 1).”
From Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms (2015) · cites this paper as [14]
In rabbits, these changes appeared as soon as 1 week after starting the high fat diet and were sustained after 3 weeks.
“Indeed, these changes appeared as soon a 1 week after starting the high fat diet and sustained after 3 weeks (20).”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [20]
Rabbits fed a high fat diet develop a rapid elevation in renal sympathetic tone, blood pressure and heart rate and impairment in baroreflex function.
“Rabbits instrumented for telemetric recording of renal sympathetic activity and hemodynamic measurements were found to develop a rapid elevation in renal sympathetic tone, blood pressure and heart rate and impairment in baroreflex function when fed a high fat diet (20).”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [20]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Stress pathways described as unchanged despite reduced stress responses
MinorThe summary says stress pathways are unchanged, but the results report substantial reductions in the blood-pressure, heart-rate, and RSNA responses to air-jet stress during the high-fat diet.
“• Sympathetic baroreflexes are impaired, but stress and chemoreflex pathways are unchanged.”
“By contrast, after the onset of the HFD (nϭ11), the MAP responses to air jet were reduced by 21% (weeks 1-2; PϽ0.05) and the tachycardia reduced by 26% to 48% (weeks 2-3) compared with baseline (PϽ0.01; Figure 2).”
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Obesity, Hypertension, and Bariatric Surgery
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Central Nervous System Dysfunction in Obesity-Induced Hypertension
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Self-citationResistin, an Adipokine with Non-Generalized Actions on Sympathetic Nerve Activity
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Potential Clinical Application of Recently Discovered Brain Mechanisms Involved in Hypertension
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Factors Responsible for Obesity-Related Hypertension
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Obesity and renovascular disease
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Recent Advances in Neurogenic Hypertension
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Central mechanisms in sympathetic nervous dysregulation in obesity
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The New Challenge of Obesity - Obesity-Associated Nephropathy
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Obesity Hypertension: Pathophysiological Role of Leptin in Neuroendocrine Dysregulation
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Regulation of the sympathetic nervous system by the kidney
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Neural Control of Non-vasomotor Organs in Hypertension
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Mechanisms mediating renal sympathetic nerve activation in obesity-related hypertension
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Self-citationEarly central cardiovagal dysfunction after high fat diet in a murine model
Strain, M. M., Espinoza, L., Fedorchak, S., Littlejohn, E. L., Andrade, M. A., Toney, G. M., & Boychuk, C. R. (2023) · Scientific Reports · doi:10.1038/s41598-023-32492-w · Cited by 11 · see citing works
Short term fat feeding rapidly increases plasma insulin but does not result in dyslipidaemia
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Self-citationComparison of sympathetic nerve activity normalization procedures in conscious rabbits
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The Carotid Body a Common Denominator for Cardiovascular and Metabolic Dysfunction?
Badoer, E. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.01069 · Cited by 11 · see citing works
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Progression of cardiovascular and endocrine dysfunction in a rabbit model of obesity
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Self-citationHypotensive Effect of Electric Stimulation of Caudal Ventrolateral Medulla in Freely Moving Rats
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High-Fat Food, Sympathetic Nerve Activity, and Hypertension
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Specific role of dietary fat in modifying cardiovascular and locomotor activity 24-h rhythms
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Self-citation
- Authors
- Armitage, J. A., Burke, S. L., Prior, L. J., Barzel, B., Eikelis, N., Lim, K., & Head, G. A.
- Affiliations
- Baker Heart and Diabetes Institute (AU)
- Venue
- Hypertension
- Published
- 2012-07
- Volume
- 60
- Issue
- 1
- Pages
- 163-171
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2097213658
- Semantic Scholar
- 5e2b7e3b4c640985cab74741b71ad3b25671cbf7
- Cited by
- 115
- References
- 38
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 9 · 2022: 3 · 2021: 4 · 2020: 11 · 2019: 5 · 2018: 4 · 2017: 7 · 2016: 12 · 2015: 17 · 2014: 12 · 2013: 18 · 2012: 2
- FWCI
- 10.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Deakin Research Online (Deakin University) (submittedVersion)
- Funders
- State Government of Victoria
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Keywords
- renal sympathetic nerve activity, high-fat diet, obesity-related hypertension, baroreflex sensitivity, hypoxia response, leptin, insulin, energy intake, arterial pressure, heart rate, hypothalamic neurons, dietary fat
- MeSH terms
- Analysis of Variance, Animals, Blood Glucose, Blood Pressure, Body Weight, Dietary Fats, Heart Rate, Hypertension, Insulin, Kidney, Male, Obesity, Rabbits, Sympathetic Nervous System, Time Factors, Baroreflex, Leptin, Adiposity, Diet, High-Fat
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