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Cited by 207Hormonal Regulation and HypertensionRenin-Angiotensin System StudiesBlood Pressure and Hypertension Studies

Aldosterone Antagonism Attenuates Obesity-Induced Hypertension and Glomerular Hyperfiltration

de Paula, Rogerio B., da Silva, Alexandre A., Hall, John E.·2004·Hypertension
DOI 10.1161/01.hyp.0000105624.68174.00
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Abstract

This study examined the importance of aldosterone (ALDO) in mediating changes in renal function and increased mean arterial pressure (MAP) during the development of dietary-induced obesity in chronically instrumented dogs. Mean arterial pressure, heart rate (HR), and cardiac output (CO) were recorded 24 hours per day in lean dogs (n=7) before and after administration of an ALDO antagonist, eplerenone (EP) (10 mg/kg twice daily), for 10 days. After 10 days of EP treatment, the dogs (n=7) were given a supplement of cooked beef fat for 5 weeks while EP was continued. An untreated group (n=6) was fed a high fat diet for 5 weeks and used as control (C). In lean dogs, EP decreased MAP from 89±4 to 84±4 mm Hg and glomerular filtration rate from 67.4±6.8 to 53.2±4.9 mL/min while inducing a small negative Na + balance (−42±12 mEq). Plasma renin activity increased from 0.4±0.1 to 2.7±0.7 ng AI/mL per hour and plasma K + increased from 4.8±0.1 to 6.1±0.3 mEq/L. After 5 weeks of a high fat diet, body weight increased 45% to 53% in EP and C obese dogs. In C dogs, MAP increased by 16±3 mm Hg, compared with only 7±1 mm Hg in EPLE dogs. Compared with untreated dogs, the EP dogs had smaller increases in CO (18±4.6% versus 43±1.5%), HR (33±5% versus 60±3%), glomerular filtration rate (19±5% versus 38±6%), and cumulative Na + balance (138±35 mEq versus 472±110 mEq) after 5 weeks of a high fat diet. Thus, EP markedly attenuated glomerular hyperfiltration, sodium retention, and hypertension associated with chronic dietary-induced obesity. These observations indicate that ALDO plays an important role in the pathogenesis of obesity hypertension.

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  • Mineralocorticoid receptor blockade markedly attenuated glomerular hyperfiltration in obese dogs fed a high-fat diet.

    “We showed that MR blockade markedly attenuated glomerular hyperfiltration in obese dogs fed an HFD47.”

    From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [47]

  • In dogs fed a high-fat diet to produce obesity, MR antagonism with eplerenone blunted sodium retention, glomerular hyperfiltration, and the development of hypertension by more than 50%.

    “In dogs fed an HFD to produce obesity, MR antagonism with eplerenone blunted sodium retention, glomerular hyperfiltration and the development of hypertension by >50%47.”

    From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [47]

  • In obese dogs, MR antagonism markedly attenuated sodium retention, hypertension, and glomerular hyperfiltration.

    “In obese dogs, for example, MR antagonism markedly attenuated sodium retention, hypertension, and glomerular hyperfiltration51 (Figure 4).”

    From Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms (2015) · cites this paper as [51]

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Research works printed but not linked: 4

  1. Miller ER, Erlinger TP, Young DR, Jehn M, Charleston J, Rhodes D, Wasan SK, Appel LJ. Results of the Diet, Exercise, and Weight Loss Intervention Trial (DEW-IT) Hypertension. 2002;40:612-618.
  2. Reisen E, Weir M, Falkner B. Hutchinson HG, Anzalone DA, Tuck ML. Lisinopril versus hydrochlorothiazide in obese hypertensive patients. Hypertension. 1997;30:140 -145.
  3. Hall JE. Renal and cardiovascular mechanisms of hypertension in obesity. Hypertension. 1994;23:381-394.
  4. Hall JE, Guyton AC, Farr BM. A single-injection technique for measuring glomerular filtration rate. Am J Physiol. 1977;232:F72-F76.

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Authors
de Paula, R. B., da Silva, A. A., & Hall, J. E.
Affiliations
  • From the Department of Physiology and Biophysics and Center of Excellence in Cardiovascular-Renal Research, The University of Mississippi Medical Center, Jackson.
  • University of Mississippi Medical Center (US)
ORCID
Hall, John E.
Venue
Hypertension
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2004-01
Volume
43
Issue
1
Pages
41-47
ISSN
  • 0194-911X (ISSN-L)
  • 1524-4563
DOI
10.1161/01.hyp.0000105624.68174.00
OpenAlex
W2097090923
Cited by
207
References
34
Citations by year
2026: 3 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 3 · 2021: 7 · 2020: 9 · 2019: 7 · 2018: 8 · 2017: 8 · 2016: 7 · 2015: 12 · 2014: 8 · 2013: 11 · 2012: 19
FWCI
6.53
Type
journal article
Language
en
Open access
closed
Locations
  • Hypertension (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (P01-HL-51971, P01HL051971)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
Keywords
aldosterone, eplerenone, obesity-related hypertension, glomerular hyperfiltration, diet-induced obesity, high-fat diet, sodium retention, plasma renin activity, plasma potassium, cardiac output, heart rate, renal function, mineralocorticoid receptor antagonists
MeSH terms
Eplerenone, Mineralocorticoid Receptor Antagonists, Animals, Dogs, Glomerular Filtration Rate, Hemodynamics, Hormones, Hypertension, Obesity, Sodium, Spironolactone

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