AT1-receptor antagonism reverses the blood pressure elevation associated with diet-induced obesity
Abstract
Previous studies in our laboratory demonstrated that rats exhibiting obesity in response to a moderately high-fat (MHF) diet developed hypertension associated with activation of the local and systemic renin-angiotensin system. In this study, we examined the effect of the angiotensin type 1 (AT 1)-receptor antagonist, losartan, on blood pressure in obesity-prone (OP) and obesity-resistant (OR) rats fed a MHF diet. Using telemetry monitoring, we characterized the evolution of blood pressure elevations during the development of obesity. Male Sprague-Dawley rats were implanted with telemetry transducers for chronic monitoring of blood pressure, and baseline measurements were obtained. Rats were then switched to the MHF diet (32% kcal as fat) and were segregated into OP and OR groups at week 5. At week 9 on the MHF diet, OP rats exhibited significantly greater 24-h mean arterial blood pressure compared with OR rats (OP: 105 ± 4 mmHg, OR: 96 ± 2 mmHg; P < 0.05). Elevations in blood pressure in OP rats were manifest as an increase in systolic pressure. Administration of losartan to all rats at week 9 resulted in a reduction in blood pressure; however, losartan had the greatest effect in OP rats (percent decrease in mean arterial pressure by losartan; OP: 19 ± 4, OR: 10 ± 2%; P < 0.05). These results demonstrate that elevations in blood pressure occur subsequent to established obesity in rats fed a high-fat diet. Moreover, these results demonstrate the ability of losartan to reverse the blood pressure increase from diet-induced obesity, supporting a primary role for the renin-angiotensin system in obesity-associated hypertension.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
An important role for AngII in stimulating renal NaCl reabsorption and in mediating obesity hypertension is supported by studies in experimental animals demonstrating that AngII receptor blockade or ACE inhibition attenuates sodium retention, volume expansion, and increased BP in obesity.
“An important role for AngII in stimulating renal NaCl reabsorption and in mediating obesity hypertension is supported by studies in experimental animals demonstrating that AngII receptor blockade or ACE inhibition attenuates sodium retention, volume expansion, and increased BP in obesity43,44.”
From Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms (2015) · cites this paper as [43]
Cites
The Kidney, Hypertension, and Obesity
Hall, J. E. (2003) · Hypertension · doi:10.1161/01.hyp.0000052314.95497.78 · Cited by 868 · see citing works
Incidence and precursors of hypertension in young adults: The Framingham offspring study
Garrison, R. J., Kannel, W. B., Stokes, J., & Castelli, W. P. (1987) · Preventive Medicine · doi:10.1016/0091-7435(87)90087-9 · Cited by 789 · see citing works
Reisin, E., Abel, R., Modan, M., Silverberg, D. S., Eliahou, H. E., & Modan, B. (1978) · New England Journal of Medicine · doi:10.1056/nejm197801052980101 · Cited by 759 · see citing works
Tuck, M. L., Sowers, J. R., Dornfeld, L., Kledzik, G. S., & Maxwell, M. H. (1981) · New England Journal of Medicine · doi:10.1056/nejm198104163041602 · Cited by 643 · see citing works
The Metabolic Syndrome in Overweight Hispanic Youth and the Role of Insulin Sensitivity
Cruz, M. L., Weigensberg, M. J., Huang, T. T. ‐., Ball, G. D. C., Shaibi, G. Q., & Goran, M. I. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031188 · Cited by 602 · see citing works
Selective breeding for diet-induced obesity and resistance in Sprague-Dawley rats
Levin, B. E., Dunn-Meynell, A. A., Balkan, B., & Keesey, R. E. (1997) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1997.273.2.r725 · Cited by 536 · see citing works
Long-Term Effects of Weight Loss and Dietary Sodium Reduction on Incidence of Hypertension
He, J., Whelton, P. K., Appel, L. J., Charleston, J. B., & Klag, M. J. (2000) · Hypertension · doi:10.1161/01.hyp.35.2.544 · Cited by 430 · see citing works
de Jongh, R. T., Serné, E. H., IJzerman, R. G., de Vries, G., & Stehouwer, C. D. A. (2004) · Circulation · doi:10.1161/01.cir.0000129772.26647.6f · Cited by 407 · see citing works
Boustany, C., Bharadwaj, K. G., Daugherty, A., Brown, D. R., Randall, D. C., & Cassis, L. A. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00265.2004 · Cited by 336 · see citing works
Self-citationObesity-induced hypertension. Renal function and systemic hemodynamics.
Hall, J. E., Brands, M. W., Dixon, W. N., & Smith, M. J. (1993) · Hypertension · doi:10.1161/01.hyp.22.3.292 · Cited by 328 · see citing works
Miller, E. R., Erlinger, T. P., Young, D. R., Jehn, M., Charleston, J., Rhodes, D., Wasan, S. K., & Appel, L. J. (2002) · Hypertension · doi:10.1161/01.hyp.0000037217.96002.8e · Cited by 319 · see citing works
Development of Hypertension in a Rat Model of Diet-Induced Obesity
Dobrian, A. D., Davies, M. J., Prewitt, R. L., & Lauterio, T. J. (2000) · Hypertension · doi:10.1161/01.hyp.35.4.1009 · Cited by 306 · see citing works
Adrenergic and Reflex Abnormalities in Obesity-Related Hypertension
Grassi, G., Seravalle, G., Dell’Oro, R., Turri, C., Bolla, G. B., & Mancia, G. (2000) · Hypertension · doi:10.1161/01.hyp.36.4.538 · Cited by 305 · see citing works
Messerli, F. H. (1981) · Archives of Internal Medicine · doi:10.1001/archinte.141.1.81 · Cited by 281 · see citing works
Obesity and hypertension: two epidemics or one?
Davy, K. P., & Hall, J. E. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00707.2003 · Cited by 280 · see citing works
Is obesity a major cause of chronic kidney disease?
Hall, J. E., Henegar, J. R., Dwyer, T. M., Liu, J., da Silva, A. A., Kuo, J. J., & Tallam, L. (2004) · Advances in Renal Replacement Therapy · doi:10.1053/j.arrt.2003.10.007 · Cited by 264 · see citing works
Oxidative Stress in a Rat Model of Obesity-Induced Hypertension
Dobrian, A. D., Davies, M. J., Schriver, S. D., Lauterio, T. J., & Prewitt, R. L. (2001) · Hypertension · doi:10.1161/01.hyp.37.2.554 · Cited by 246 · see citing works
Bloem, L. J., Manatunga, A. K., Tewksbury, D. A., & Pratt, J. H. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117803 · Cited by 244 · see citing works
Mechanisms of Abnormal Renal Sodium Handling in Obesity Hypertension
Hall, J. (1997) · American Journal of Hypertension · doi:10.1016/s0895-7061(97)00075-7 · Cited by 213 · see citing works
Messerli, F. H. (1981) · Archives of Internal Medicine · doi:10.1001/archinte.1981.00340010073016 · Cited by 210 · cited 1× · see citing works
“A heightened heart rate has been described as a common characteristic of obese hypertensive subjects (12, 20, 35, 37).”
BackgroundJones, D. W., Kim, J. S., Andrew, M. E., Kim, S. J., & Hong, Y. P. (1994) · Journal of Hypertension · doi:10.1097/00004872-199412000-00018 · Cited by 191 · cited 1× · see citing works
“In fact, excess adiposity is among the best predictor for subsequent heightened blood pressure (8, 17, 24, 26, 27).”
BackgroundObesity-associated hypertension and kidney disease
Hall, J. E., Kuo, J. J., da Silva, A. A., de Paula, R. B., Liu, J., & Tallam, L. (2003) · Current Opinion in Nephrology and Hypertension · doi:10.1097/00041552-200303000-00011 · Cited by 187 · see citing works
The Puzzle of Hypertension in African-Americans
Cooper, R. S., Rotimi, C. N., & Ward, R. H. (1999) · Scientific American · doi:10.1038/scientificamerican0299-56 · Cited by 176 · see citing works
Blood Pressure Is Associated With Body Mass Index in Both Normal and Obese Children
He, Q., Ding, Z. Y., Fong, D., & KARLBERG, J. P. E. (2000) · Hypertension · doi:10.1161/01.hyp.36.2.165 · Cited by 175 · see citing works
Increased Adipose Angiotensinogen Gene Expression in Human Obesity
van Harmelen, V., Ariapart, P., Hoffstedt, J., Lundkvist, I., Bringman, S., & Arner, P. (2000) · Obesity Research · doi:10.1038/oby.2000.40 · Cited by 172 · see citing works
Plasma Angiotensinogen Concentrations in Obese Patients
Umemura, S. (1997) · American Journal of Hypertension · doi:10.1016/s0895-7061(97)00053-8 · Cited by 171 · see citing works
ACE, angiotensinogen and obesity: a potential pathway leading to hypertension
Cooper, R., McFarlane‐Anderson, N., Bennett, F., Wilks, R., Puras, A., Tewksbury, D. A., Ward, R. H., & Forrester, T. (1997) · Journal of Human Hypertension · doi:10.1038/sj.jhh.1000391 · Cited by 162 · see citing works
Reisin, E., Weir, M. R., Falkner, B., Hutchinson, H. G., Anzalone, D. A., & Hypertension, M. L. T. F. T. T. I. O. P. W. (1997) · Hypertension · doi:10.1161/01.hyp.30.1.140 · Cited by 158 · see citing works
Role of sympathetic nervous system and neuropeptides in obesity hypertension
Hall, J. E., BRANDS, M., Hildebrandt, D. A., Kuo, J. J., & Fitzgerald, S. M. (2000) · Brazilian Journal of Medical and Biological Research · doi:10.1590/s0100-879x2000000600001 · Cited by 149 · see citing works
Initiation and perpetuation of obesity and obesity resistance in rats
Levin, B. E., Hogan, S. P., & Sullivan, A. C. (1989) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1989.256.3.r766 · Cited by 148 · see citing works
Sympathetic activity and blood pressure are tightly coupled at 0.4 Hz in conscious rats
Brown, D. R., Brown, L. V., Patwardhan, A. R., et al. (1994) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1994.267.5.r1378 · Cited by 139 · see citing works
Self-citationAltered sympathetic activity during development of diet-induced obesity in rat
Levin, B. E., Triscari, J. M., & Sullivan, A. C. (1983) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1983.244.3.r347 · Cited by 133 · see citing works
Egan, B. M., Stepniakowski, K., & Goodfriend, T. L. (1994) · PubMed · doi:10.1016/0895-7061(94)p1710-h · Cited by 114 · see citing works
van Harmelen, V, Elizalde, M., Ariapart, P., Bergstedt-Lindqvist, S., Reynisdottir, S., Hoffstedt, J., Lundkvist, I., Bringman, S., & Arner, P. (2000) · International Journal of Obesity · doi:10.1038/sj.ijo.0801217 · Cited by 114 · see citing works
Differential stress responsivity in diet-induced obese and resistant rats
Levin, B. E., Richard, D., Michel, C., & Servatius, R. J. (2000) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2000.279.4.r1357 · Cited by 106 · see citing works
Distribution of angiotensin II receptors in rat and human adipocytes.
Crandall, D. L., Herzlinger, H. E., Saunders, B., Armellino, D. C., & Kral, J. G. (1994) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)40079-3 · Cited by 100 · see citing works
Resistance to diet-induced obesity: food intake, pancreatic sympathetic tone, and insulin
Levin, B. E., Triscari, J. M., Hogan, S. P., et al. (1987) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1987.252.3.r471 · Cited by 95 · see citing works
Licata, G., Scaglione, R., Ganguzza, A., Corrao, S., Donatelli, M., Parrinello, G., Oichiara, M. A., Merlino, G., & Cecala, M. C. (1994) · American Journal of Hypertension · doi:10.1093/ajh/7.4.314 · Cited by 94 · see citing works
Egan, B. M., Stepniakowski, K. T., & Goodfriend, T. L. (1994) · American Journal of Hypertension · doi:10.1093/ajh/7.10.886 · Cited by 94 · see citing works
Angiotensinogen levels and obesity in four black populations
Cooper, R., Forrester, T., Ogunbiyi, O. J., & Muffinda, J. (1998) · Journal of Hypertension · doi:10.1097/00004872-199816050-00003 · Cited by 89 · see citing works
Hemodynamic Alterations in Hypertensive Obese Rabbits
Carroll, J. F., Huang, M., Hester, R. L., Cockrell H., K., & Mizelle, L. (1995) · Hypertension · doi:10.1161/01.hyp.26.3.465 · Cited by 67 · see citing works
Obesity, hypertension, and sympathetic nervous system activity
Corry, D. B., & Tuck, M. L. (1999) · Current Hypertension Reports · doi:10.1007/s11906-999-0005-x · Cited by 64 · see citing works
Obesity and Essential Hypertension
Messerli, F. H., Ventura, H. O., Reisin, E., Dreslinski, G. R., Dunn, F. G., & Frohlich, E. D. (2015) · Contributions to nephrology · doi:10.1159/000406429 · Cited by 57 · see citing works
Control of differentiation-induced calbindin-D9kgene expression in Caco-2 cells by cdx-2 and HNF-1α
Wang, L., Kłopot, A., Freund, J., et al. (2004) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00121.2004 · Cited by 37 · see citing works
Dietary obesity and neonatal sympathectomy. I. Effects on body composition and brown adipose
Levin, B. E., Triscari, J. M., Marquet, E., et al. (1984) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1984.247.6.r979 · Cited by 28 · see citing works
Burgess, D. E., Randall, D. C., Speakman, R. O., et al. (2003) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00002.2002 · Cited by 12 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms
Hall, J. E., do Carmo, J. M., da Silva, A. A., Wang, Z., & Hall, M. E. (2015) · Circulation Research · doi:10.1161/circresaha.116.305697 · Cited by 1,360 · see citing works
Putnam, K., Shoemaker, R., Yiannikouris, F., & Cassis, L. A. (2012) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00796.2011 · Cited by 273 · see citing works
Self-citationHypertension: Physiology and Pathophysiology
Hall, J. E., Granger, J. P., do Carmo, J. M., da Silva, A. A., Dubinion, J., George, E., Hamza, S., Speed, J., & Hall, M. E. (2012) · Comprehensive Physiology · doi:10.1002/cphy.c110058 · Cited by 232 · see citing works
Systemic and Renal-Specific Sympathoinhibition in Obesity Hypertension
Lohmeier, T. E., Iliescu, R., Liu, B., Henegar, J. R., Maric-Bilkan, C., & Irwin, E. D. (2012) · Hypertension · doi:10.1161/hypertensionaha.111.185074 · Cited by 130 · see citing works
Cardiovascular Function in a Rat Model of Diet-Induced Obesity
Carroll, J. F., Zenebe, W. J., & Strange, T. B. (2006) · Hypertension · doi:10.1161/01.hyp.0000224147.01024.77 · Cited by 129 · see citing works
Prolonged Activation of the Baroreflex Abolishes Obesity-Induced Hypertension
Lohmeier, T. E., Dwyer, T. M., Irwin, E. D., Rossing, M. A., & Kieval, R. S. (2007) · Hypertension · doi:10.1161/hypertensionaha.107.087874 · Cited by 118 · see citing works
Renal denervation for the treatment of resistant hypertension: review and clinical perspective
Iliescu, R., Lohmeier, T. E., Tudorancea, I., Laffin, L., & Bakris, G. L. (2015) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00246.2015 · Cited by 50 · see citing works
Perinatal Exposure to Western Diet Programs Autonomic Dysfunction in the Male Offspring
Mukerjee, S., Zhu, Y., Zsombok, A., Mauvais-Jarvis, F., Zhao, J., & Lazartigues, E. (2018) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-017-0502-4 · Cited by 18 · see citing works
- Authors
- Boustany, C. M., Brown, D. R., Randall, D. C., & Cassis, L. A.
- Affiliations
- University of Kentucky (US)
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2005-07
- Volume
- 289
- Issue
- 1
- Pages
- R181-R186
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2059519099
- Cited by
- 76
- References
- 46
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 6 · 2019: 1 · 2018: 1 · 2017: 4 · 2016: 6 · 2015: 4 · 2014: 6 · 2013: 3 · 2012: 9
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl073085-13)
- National Heart, Lung, and Blood Institute (HL-73085)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- losartan, diet-induced obesity, obesity-related hypertension, renin-angiotensin system, high-fat diet, obesity-prone rats, obesity-resistant rats, blood pressure, systolic blood pressure, mean arterial pressure
- MeSH terms
- Animals, Blood Pressure, Dietary Fats, Disease Susceptibility, Dose-Response Relationship, Drug, Male, Obesity, Rats, Sprague-Dawley, Losartan, Receptor, Angiotensin, Type 1, Angiotensin II Type 1 Receptor Blockers, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
