Aldosterone antagonism attenuates obesity-induced hypertension and glomerular hyperfiltration

Hypertension. 2004 Jan;43(1):41-7. doi: 10.1161/01.HYP.0000105624.68174.00. Epub 2003 Nov 24.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Dogs
  • Eplerenone
  • Glomerular Filtration Rate / drug effects
  • Hemodynamics / drug effects
  • Hormones / blood
  • Hypertension / drug therapy*
  • Hypertension / etiology
  • Hypertension / physiopathology
  • Mineralocorticoid Receptor Antagonists / therapeutic use*
  • Obesity / complications*
  • Sodium / urine
  • Spironolactone / analogs & derivatives*
  • Spironolactone / therapeutic use*

Substances

  • Hormones
  • Mineralocorticoid Receptor Antagonists
  • Spironolactone
  • Eplerenone
  • Sodium