title: Aldosterone antagonism attenuates obesity-induced hypertension and glomerular hyperfiltration.
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.
authors.affiliation: Department of Physiology and Biophysics and Center of Excellence in Cardiovascular-Renal Research, The University of Mississippi Medical Center, Jackson 39216-4505, USA.
authors.forename: Rogerio B
authors.initials: RB
authors.lastname: de Paula
authors.forename: Alexandre A
authors.initials: AA
authors.lastname: da Silva
authors.forename: John E
authors.initials: JE
authors.lastname: Hall
mesh_terms: D000818:Animals; D004285:Dogs; D000077545:Eplerenone; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006728:Hormones / Q000097:blood; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D009765:Obesity / Q000150:complications*; D012964:Sodium / Q000652:urine; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use*
chemical_list: D006728:Hormones; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone; D012964:Sodium