Insulin-Induced Hypertension in Rats Depends on an Intact Renin-Angiotensin System

Abstract

Abstract This study tested the dependence of insulin-induced hypertension in rats on a functional renin-angiotensin system. Rats were instrumented with chronic artery and vein catheters and housed in metabolic cages. After acclimation, 10 rats began receiving the angiotensin-converting enzyme inhibitor (ACEI) benazepril at 1.8 mg · kg −1 · d −1 via a continuous intravenous infusion that was maintained throughout the study; 8 control rats received vehicle. Four days after starting ACEI or vehicle, all rats entered a 5-day control period that was followed by a 7-day insulin infusion at 1.5 mU · kg −1 · min −1 . Glucose was coinfused at 22 mg · kg −1 · min −1 to prevent hypoglycemia. Insulin infusion in control rats increased mean arterial pressure (MAP; measured 24 h/d) from an average of 101±1 to 113±2 mm Hg on day 1; MAP averaged 110±1 mm Hg for the 7-day infusion period. Glomerular filtration rate decreased, although not significantly, from 2.7±0.1 to 2.1±0.2 mL/min on day 3. Chronic ACEI decreased baseline MAP from an average of 97±1 to 79±1 mm Hg and markedly attenuated the increase in MAP during insulin. MAP averaged 81±1 mm Hg for the 7-day period and increased significantly, to 85±2 mm Hg, only on day 3. Likewise, the tendency for glomerular filtration rate to decrease was blunted. These results indicate that insulin-induced hypertension in rats depends on angiotensin II and suggest that a reduction in glomerular filtration rate contributes to the shift in pressure natriuresis.