Chronic baroreflex activation restores spontaneous baroreflex control and variability of heart rate in obesity-induced hypertension
Open accessAbstract
The sensitivity of baroreflex control of heart rate is depressed in subjects with obesity hypertension, which increases the risk for cardiac arrhythmias. The mechanisms are not fully known, and there are no therapies to improve this dysfunction. To determine the cardiovascular dynamic effects of progressive increases in body weight leading to obesity and hypertension in dogs fed a high-fat diet, 24-h continuous recordings of spontaneous fluctuations in blood pressure and heart rate were analyzed in the time and frequency domains. Furthermore, we investigated whether autonomic mechanisms stimulated by chronic baroreflex activation and renal denervation—current therapies in patients with resistant hypertension, who are commonly obese—restore cardiovascular dynamic control. Increases in body weight to ∼150% of control led to a gradual increase in mean arterial pressure to 17 ± 3 mmHg above control (100 ± 2 mmHg) after 4 wk on the high-fat diet. In contrast to the gradual increase in arterial pressure, tachycardia, attenuated chronotropic baroreflex responses, and reduced heart rate variability were manifest within 1–4 days on high-fat intake, reaching 130 ± 4 beats per minute (bpm) (control = 86 ± 3 bpm) and ∼45% and <20%, respectively, of control levels. Subsequently, both baroreflex activation and renal denervation abolished the hypertension. However, only baroreflex activation effectively attenuated the tachycardia and restored cardiac baroreflex sensitivity and heart rate variability. These findings suggest that baroreflex activation therapy may reduce the risk factors for cardiac arrhythmias as well as lower arterial pressure.
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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 [179]
In dogs, the reductions in cardiac baroreflex sensitivity and heart rate variability intensified with progressive weight gain and hypertension.
“In dogs, marked reductions in 24-hour cardiac baroreflex sensitivity and HR variability occurred within a few days of starting an HFD, before appreciable weight gain or large BP increases, although these responses intensified with progressive weight gain and hypertension179.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [179]
In dogs, marked reductions in 24-hour cardiac baroreflex sensitivity and heart rate variability occurred within a few days of starting a high-fat diet, before appreciable weight gain or large blood pressure increases.
“In dogs, marked reductions in 24-hour cardiac baroreflex sensitivity and HR variability occurred within a few days of starting an HFD, before appreciable weight gain or large BP increases, although these responses intensified with progressive weight gain and hypertension179.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [179]
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BackgroundLoria, A. S., & Osborn, J. L. (2017) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00591.2016 · Cited by 18 · see citing works
“In light that arterial baroreflex sensitivity is blunted with the initiation of hypertension (19, 43), our data indicate that exposure to MatSep may lead to altered baroreflex sensitivity and predispose rats to impaired blood pressure control during adult life.”
BackgroundWu, J., Tong, L., Hu, L., Xia, C., Li, M., Chen, Q., Chen, F., & Du, D. (2018) · Hypertension Research · doi:10.1038/s41440-018-0105-6 · Cited by 18 · see citing works
Clemmer, J. S., Pruett, W. A., Hester, R. L., Iliescu, R., & Lohmeier, T. E. (2018) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00302.2018 · Cited by 15 · see citing works
“In heart failure, increased sympathetic and decreased parasympathetic activity play a major role in disease progression, and a particularly favorable effect of baroreflex activation is that it has unique central actions to substantially correct this imbalance (6, 17, 22).”
BackgroundInfluentialSelf-citationEffects of low-level carotid baroreflex stimulation on atrial electrophysiology
Dai, M., Bao, M., Liao, J., Yu, L., Tang, Y., Huang, H., Wang, X., & Huang, C. (2015) · Journal of Interventional Cardiac Electrophysiology · doi:10.1007/s10840-015-9976-5 · Cited by 14 · see citing works
“In dogs, with obesity-induced hypertension, chronic CBS was validated to shift cardiac autonomic balance in favor of vagal activity [30].”
BackgroundReduced Renal Mass, Salt-Sensitive Hypertension Is Resistant to Renal Denervation
Tudorancea, I., Lohmeier, T. E., Alexander, B. T., Pieptu, D., Șerban, D. N., & Iliescu, R. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00455 · Cited by 14 · see citing works
“Spectral analysis was performed using the Fast Fourier Transform, as we previously described (Iliescu et al., 2013).”
MethodSelf-citationTohyama, T., Hosokawa, K., Saku, K., Oga, Y., Tsutsui, H., & Sunagawa, K. (2019) · Hypertension · doi:10.1161/hypertensionaha.119.13673 · Cited by 13 · see citing works
“Meanwhile, they also demonstrated that cBAT did not reduce BPV in obese hypertensive dogs.(29) In clinical observation, Floyd et al(30) reported that cBAT”
BackgroundResultObesity and diabetes in heart disease in women
Fatade, Y. A., Dave, E. K., Vatsa, N., Crumbs, T., Calhoun, A. E., Sharma, A., SHUFELT, C. L., & Mehta, P. K. (2024) · Metabolism and Target Organ Damage · doi:10.20517/mtod.2023.30 · Cited by 12 · see citing works
The Baroreceptor as a Therapeutic Target for Heart Failure
Gronda, E., Lovett, E. G., Tarascio, M., Georgakopoulos, D., Grassi, G. M., & Vanoli, E. (2014) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-014-9546-8 · Cited by 12 · see citing works
“Important in light of clinical HF, it has been shown that chronic BATof obese, hypertensive canines ameliorates the attendant tachycardia and restores baseline BRS and heart rate variability [50].”
BackgroundSierra, À., Calhoun, D. A., Vinyoles, E., Banegas, J. R., de la Cruz, J. J., Gorostidi, M., Segura, J., & Ruilope, L. M. (2014) · Journal of Human Hypertension · doi:10.1038/jhh.2013.135 · Cited by 12 · see citing works
Baroreflex Activation Therapy in Congestive Heart Failure: Novel Findings and Future Insights
Grassi, G. M., Brambilla, G., Pizzala, D. P., & Seravalle, G. (2016) · Current Hypertension Reports · doi:10.1007/s11906-016-0667-0 · Cited by 10 · see citing works
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Baroreflex deficiency aggravates atherosclerosis via α7 nicotinic acetylcholine receptor in mice
Chen, L., Liu, D., Zhang, X., Zhang, E.-H., Liu, C., Su, D., & Cai, G. (2016) · Vascular Pharmacology · doi:10.1016/j.vph.2016.08.008 · Cited by 9 · see citing works
Baroreflex activation therapy through electrical carotid sinus stimulation
Jordan, J., Tank, J., Heusser, K., & Reuter, H. (2024) · Autonomic Neuroscience · doi:10.1016/j.autneu.2024.103219 · Cited by 6 · see citing works
“In addition to attenuating sympathetic efferent activity, electrical carotid sinus stimulation augmented heart rate variability and baroreflex heart rate control (Iliescu et al., 2013).”
Effects of carotid baroreceptor stimulation on aortic remodeling in obese rats
Yu, Q., Shu, L., Wang, L., Gao, K., Wang, J., Dai, M., Cao, Q., Zhang, Y., Luo, Q., Hu, B., et al. (2021) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2021.01.021 · Cited by 5 · see citing works
Jordan, J. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2013.268078 · Cited by 5 · see citing works
“Moreover, electrical carotid sinus stimulation and surgical renal denervation improved blood pressure in dogs with established obesity-associated arterial hypertension (Iliescu et al. 2013).”
BackgroundNatali, L. H., Troiano, J. A., Potje, S. R., Dias, D. P. M., & Antoniali, C. (2022) · Pregnancy Hypertension · doi:10.1016/j.preghy.2022.05.002 · Cited by 5 · see citing works
Cao, Z., Wang, J., Pang, N., Lin, Y., & Liu, X. (2025) · Cardiovascular Diabetology – Endocrinology Reports · doi:10.1186/s40842-025-00255-3 · Cited by 3 · see citing works
“Consequently, heart rate and myocardial contractility increase, renal vasoconstriction intensifies, and renin release is stimulated, collectively contributing to elevated blood pressure [36–38].”
Baroreflex Activation Therapy in Heart Failure
Grassi, G. M., & Lovett, E. G. (2015) · Springer eBooks · doi:10.1007/978-3-319-24993-3_12 · Cited by 3 · see citing works
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“While carotid sinus stimulation (CSS) does not impede but rather restores spontaneous baroreflex control in a canine model of obesity-induced hypertension (11), whether CSS impedes the dynamic characteristics of the unstimulated arterial baroreflex remains unknown.”
BackgroundTudorancea, I., Șerban, I. L., Șerban, D. N., Costache-Enache, I.-I., Cătălin, C., Naum, A. S., & Iliescu, R. (2025) · Scientific Reports · doi:10.1038/s41598-024-84218-1 · Cited by 2 · see citing works
Self-citationAngle, J. F., Prince, E. A., Matsumoto, A. H., Lohmeier, T. E., Roberts, A. M., Misra, S., Razavi, M. K., Katholi, R. E., Sarin, S. N., Sica, D. A., et al. (2014) · Journal of Vascular and Interventional Radiology · doi:10.1016/j.jvir.2013.12.572 · Cited by 2 · see citing works
“Tachyarrhythmias and Sympathetic Hyperactivity The autonomic nervous system modulates cardiac electrophysiology and has a profound effect on cardiac automaticity (59).”
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“The advantages of HRV as a main methodological method and instrument developed, researched and applied in the fields of physiology, psycho-physiology, cardiology, preventive and occupational medicine are that it may screen and diagnose the major physiological and pathophysiological mechanisms controlling the cardiovas…”
MethodWhite, D. W., & Fernhall, B. (2015) · Molecular and translational medicine · doi:10.1007/978-3-319-17076-3_9 · Cited by 1 · see citing works
Carotid Baroreceptor Stimulation
Jordan, J., Tank, J., & Reuter, H. (2019) · Updates in hypertension and cardiovascular protection · doi:10.1007/978-3-319-93320-7_23 · Cited by 1 · see citing works
Tudorancea, I., Mitu, F., Petriş, A. O., Şerban, D., Șerban, I. L., Iliescu, R., & Pieptu, D. (2018) · The Medical-Surgical Journal
Self-citationBLOOD PRESSURE LOWERING EFFECTS OF CENTRAL TNF- BLOCKADE DEPENDS ON FUNCTIONAL LEPTIN SIGNALING
Tudorancea, I. (2023) · The Medical-Surgical Journal · doi:10.22551/msj.2023.03.13
“As we previously described (17), the original daily BP signal sampled at 2000 Hz was analyzed in the frequency domain using the implementation of the LabChart ® software based on the Fast Fourier Trans-form algorithm.”
BackgroundMethodInfluentialSelf-citationZhen, C., Li, R., Ma, T., Xu, A., Bian, Y., & Li, B. (2024) · Food Science and Human Wellness · doi:10.26599/fshw.2024.9250148
Popa, I. P., Haba, M. Ș. C., Costache-Enache, I.-I., Iliescu, R., Loghin, C., Čurila, K., & Tudorancea, I. (2026) · Scientific Reports · doi:10.1038/s41598-026-64234-z
“Cardiac BRS was quantified using the sequence method, as previously described 13 .”
Self-citation
- Authors
- Iliescu, R., Tudorancea, I., Irwin, E. D., & Lohmeier, T. E.
- Affiliations
- University of Mississippi Medical Center (US)
- Cardiovascular Research Department, “Gr. T. Popa” Center for Biomedical Research and the University of Medicine and Pharmacy “Gr. T. Popa,” Iasi, Romania; and
- North Memorial Medical Center (US)
- Corresponding author
- Lohmeier, Thomas E.
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2013-10-01
- Volume
- 305
- Issue
- 7
- Pages
- H1080-H1088
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- PMC
- PMC3798752
- OpenAlex
- W2102626436
- Cited by
- 46
- References
- 67
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 6 · 2017: 2 · 2016: 3 · 2015: 6 · 2014: 7 · 2013: 1
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL‐51971, P01HL051971)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Keywords
- baroreflex activation therapy, obesity-related hypertension, baroreflex sensitivity, heart rate variability, tachycardia, high-fat diet, renal denervation, resistant hypertension, arrhythmia risk, autonomic dysfunction, blood pressure regulation, dogs
- MeSH terms
- Animals, Disease Models, Animal, Dogs, Electric Stimulation Therapy, Heart Rate, Hypertension, Kidney, Male, Obesity, Sympathectomy, Tachycardia, Time Factors, Baroreflex, Arterial Pressure
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