Characterization of a new model for the study of pressure-natriuresis in the rat
Abstract
The acute relationships between the urinary excretion of sodium and water and renal perfusion pressure were characterized in the rat using a new in vivo model of pressure diuresis. Neural and hormonal influences on the kidney were held constant by denervating the kidney and by maintaining fixed high plasma levels of vasopressin, aldosterone, corticosterone, and norepinephrine levels by intravenous infusion. Renal perfusion pressure (RPP) was varied above and below control using specially designed aortic clamps. Increasing RPP within the autoregulatory range from 90 to 160 mmHg produced 5- to 20-fold increases in urine flow and sodium excretion with no detectable changes in glomerular filtration rate, renal blood flow, or peritubular capillary pressure. The slope of the line relating urine flow and RPP averaged 2 microliter X min-1 X kidney-1 X mmHg-1 rise in RPP. If RPP was first lowered to 90 mmHg, urine flow could be doubled by increasing RPP by as little as 5 mmHg. Uninephrectomy 7-12 days before an experiment did not alter the renal pressure diuresis relationship. The presence of intact renal nerves, however, was found to shift the relationship between urine flow and RPP to the right. The magnitude of the response produced by elevations in pressure using this new model of pressure diuresis was greater than when RPP was increased using carotid occlusion or epinephrine infusion as in previous studies. The results indicate that small changes in arterial pressure may have a greater influence on sodium and water excretion than has been previously recognized.
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Renal parenchymal nociceptive sensory nerves respond to a renal injury signal by projecting to the hypothalamus to increase central sympathetic outflow.
“The first, of the renal parenchyma and bearing nociceptive receptors, respond to a renal injury signal by projecting to the hypothalamus to increase central sympathetic outflow95–99.”
From The Sympathetic Nervous System Alterations in Human Hypertension (2015) · cites this paper as [98]
Renal sympathetic denervation shifts the renal pressure-natriuresis curve to the left, promoting urinary sodium excretion and lowering blood pressure.
“Renal sympathetic denervation shifts the renal pressure-natriuresis curve to the left, promoting urinary sodium excretion and lowering of blood pressure94–98.”
From The Sympathetic Nervous System Alterations in Human Hypertension (2015) · cites this paper as [98]
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“At these concentrations and this infusion rate, plasma levels of these hormones were reported to be elevated 8- to 10-fold compared with normal values obtained in conscious rats.(15) The cocktail and infusion rate were designed to volume expand the rats and minimize reflex hormonal adjustments to the kidney, which may…”
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“17 ng zkg21 zmin21), aldosterone (66 ng zkg21 zmin21), and norepinephrine (333 ng zkg21 zmin21) were fixed at high physiological levels by an intravenous infusion of a hormone cocktail at a rate of 1 ml z100 g21 zh21 (22).”
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Self-citationPressure diuresis and natriuresis in DOCA-salt mice
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“Vasopressin (52 pg/min), aldosterone (20 ng/min), norepinephrine (100 ng/min) and hydrocortisol (20 g/min) were included in the infusion solution to minimize any potential differences in the circulating levels of these hormones between the strains (22).”
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“An acute increase in blood pressure was induced by increasing total peripheral vascular resistance, as suggested by Roman and Cowley (13) and Yip et al. (16).”
BackgroundA study of the renal actions of amlodipine in the normotensive and spontaneously hypertensive rat
Johns, E. J. (1988) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1988.tb11532.x · Cited by 26 · see citing works
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“The renal function studies were undertaken at constant renal perfusion pressure, because pressure at the kidney itself can directly determine the level of sodium and water excretion (24).”
Background4 Control of blood and extracellular volume
Cowley, A. W., & Roman, R. J. (1989) · Baillière s Clinical Endocrinology and Metabolism · doi:10.1016/s0950-351x(89)80007-2 · Cited by 24 · see citing works
Self-citationSex differences in pressure diuresis/natriuresis in rabbits
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“Interestingly, renal sympathetic denervation shifts the renal pressure–natriuresis curve to the left, promoting urinary sodium excretion and lowering of blood pressure (BP) [7].”
BackgroundDownstream Shift in Sodium Pump Activity along the Nephron during Acute Hypertension
Magyar, C. E., Zhang, Y., Holstein‐Rathlou, N., et al. (2001) · Journal of the American Society of Nephrology · doi:10.1681/asn.v12112231 · Cited by 23 · see citing works
Renal Sympathetic Neural Mechanisms as Intermediate Phenotype in Spontaneously Hypertensive Rats
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Effects of Renal Medullary and Intravenous Norepinephrine on Renal Antihypertensive Function
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Diuretic response to acute hypertension is blunted during angiotensin II clamp
Leong, P. K. K., Zhang, Y., Yang, L. E., Holstein‐Rathlou, N., & McDonough, A. A. (2002) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00089.2002 · Cited by 22 · see citing works
“Because of the lack of changes in RBF, Roman and Cowley (27) attributed the transient increase to the washout of preexisting urine in the kidney rather than a genuine elevation in GFR.”
BackgroundMethodInfluentialTakenaka, T., Suzuki, H., Furukawa, T., et al. (1990) · Clinical and Experimental Hypertension · doi:10.3109/10641969009073525 · Cited by 22 · see citing works
Masilamani, S. M. E., Hobbs, G. R., & Baylis, C. (1998) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(98)70384-9 · Cited by 22 · see citing works
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“, 21), often using the model of the anesthetized rats infused with vasopressin, aldosterone, norepinephrine, and hydrocortisone (29).”
MethodThe current status of renal denervation for the treatment of arterial hypertension
Lauder, L., Böhm, M., & Mahfoud, F. (2021) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2021.02.005 · Cited by 20 · see citing works
20-Hydroxyeicosatetraenoic acid and renal function in Lyon hypertensive rats
Messer-Létienne, I., Bernard, N., Roman, R. J., et al. (1999) · European Journal of Pharmacology · doi:10.1016/s0014-2999(99)00470-7 · Cited by 20 · see citing works
Self-citationRole of ANG II in mediating somatosensory-induced renal nerve-dependent antinatriuresis in the rat
Huang, C., & Johns, E. J. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.275.1.r194 · Cited by 20 · see citing works
“The decreased fluid excretion during losartan was most probably due to the influence of the large fall in pressure at the kidney acting via the mechanisms described above (33).”
BackgroundNakamura, T., Alberola, A. M., Salazar, F. J., Saito, Y., Kurashina, T., Granger, J. P., & Nagai, R. (1997) · The Nephron journals/Nephron journals · doi:10.1159/000044889 · Cited by 18 · see citing works
Kinoshita, Y., & Knox, F. G. (1990) · Circulation Research · doi:10.1161/01.res.66.5.1184 · Cited by 19 · see citing works
Fan, F., Chen, C. C. A., Zhang, J., et al. (2015) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00311.2015 · Cited by 18 · see citing works
Self-citationRenal sympathetic nerves – what have they got to do with cardiovascular disease?
Barrett, C. J. (2015) · Experimental Physiology · doi:10.1113/expphysiol.2014.080176 · Cited by 18 · see citing works
Huang, C., Davis, G., & Johns, E. J. (1994) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1994.tb14031.x · Cited by 18 · see citing works
Shimada, S., Abais‐Battad, J. M., Alsheikh, A. J., Yang, C., Stumpf, M., Kurth, T. M., Mattson, D. L., & Cowley, A. W. (2020) · Hypertension · doi:10.1161/hypertensionaha.120.15295 · Cited by 20 · see citing works
“Both red-cell flux and peritubular capillary pressures of the superficial cortical microvessels have been found to be well autoregulated in the classic sense that they remain unchanged in response to acute step changes of RPP.(37) And yet, we and others have observed renal microvessel rarefaction in both the Dahl S an…”
BackgroundInfluentialSelf-citationMesser-Létienne, I. (1999) · American Journal of Hypertension · doi:10.1016/s0895-7061(98)00256-8 · Cited by 18 · see citing works
“Surgical Preparation The left kidney was surgically prepared for study of the pressure-natriuresis response with neural and hormonal influences controlled as previously described.(18) Seven to ten days before the experiment, the right kidney and adrenal gland were removed.”
MethodDehmel, B., Mervaala, E. M. A., Lippoldt, A., Groß, V., Bohlender, J. E., Ganten, D., & Luft, F. C. (1998) · Journal of the American Society of Nephrology · doi:10.1681/asn.v9122212 · Cited by 18 · see citing works
Blunted pressure natriuretic response in the old rat: Participation of the renal nerves
Masilamani, S. M. E., Zhang, X.-Z., & Baylis, C. (1998) · American Journal of Kidney Diseases · doi:10.1016/s0272-6386(98)70024-1 · Cited by 18 · see citing works
Pressure Natriuresis in Salt-Sensitive and Salt-Resistant Sabra Rats
Groß, V., Lippoldt, A., Yagil, C., et al. (1997) · Hypertension · doi:10.1161/01.hyp.29.6.1252 · Cited by 18 · see citing works
Waldman, B. M., Augustyniak, R. A., Chen, H., et al. (2017) · Integrated Blood Pressure Control · doi:10.2147/ibpc.s147122 · Cited by 17 · see citing works
“Excretory function The higher urinary sodium excretion rate by the unclipped kidney but not the clipped kidney in the sedentary 2K-1C group reflects the substantial influence that renal perfusion pressure exerts via pressure natriuresis.(48) Our findings are consistent with studies showing that acutely elevated levels…”
Effect of Renal Denervation on the Development of Cellophane-Wrap Hypertension in Rabbits
Kline, R. L., Denton, K. M., & Anderson, W. P. (1986) · Clinical and Experimental Hypertension · doi:10.3109/10641968609044090 · Cited by 17 · see citing works
Effect of enalapril treatment on the pressure-natriuresis curve in spontaneously hypertensive rats.
McLennan, G. P., Kline, R. L., & Mercer, P. F. (1991) · Hypertension · doi:10.1161/01.hyp.17.1.54 · Cited by 17 · see citing works
“This model was designed to minimize neural or hormonal reflex adjustments to the kidney, which may result from using clamps to increase or decrease renal artery pressure.(15) On average, surgery was completed within 90 minutes, at which time the abdomen was bathed in 0.”
MethodResultRegulation of Renal Hemodynamics and Function by RGS2
Osei‐Owusu, P., Owens, E. A., Li, J., Reis, J. S., Forrester, S. J., Kawai, T., Eguchi, S., Singh, H., & Blumer, K. (2015) · PLoS ONE · doi:10.1371/journal.pone.0132594 · Cited by 16 · see citing works
- Authors
- Roman, R. J., & Cowley, A. W.
- Venue
- American Journal of Physiology-Renal Physiology
- Publisher
- American Physiological Society
- Published
- 1985-02-01
- Volume
- 248
- Issue
- 2
- Pages
- F190-F198
- ISSN
- 1522-1466 (ISSN-L)
- 1931-857X
- OpenAlex
- W1798432044
- Cited by
- 176
- References
- 0
- Citations by year
- 2024: 2 · 2023: 3 · 2022: 2 · 2021: 6 · 2020: 5 · 2019: 1 · 2017: 3 · 2016: 2 · 2015: 13 · 2014: 10 · 2013: 5 · 2012: 2
- FWCI
- 4.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Renal Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-29587-01, R37HL036279)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Renal and Vascular Pathologies
- Keywords
- pressure natriuresis, pressure diuresis, renal perfusion pressure, sodium excretion, water excretion, renal autoregulation, renal denervation, renal nerves, unilateral nephrectomy, urine flow, renal blood flow, glomerular filtration rate, vasopressin, aldosterone, corticosterone, norepinephrine
- MeSH terms
- Animals, Blood Pressure, Capillaries, Diuresis, Glomerular Filtration Rate, Homeostasis, Hormones, Kidney, Male, Natriuresis, Nephrectomy, Perfusion, Physiology, Rats, Inbred Strains, Rats
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