Aldosterone Antagonism Attenuates Obesity-Induced Hypertension and Glomerular Hyperfiltration

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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.