Regulation of Cardiovascular Signaling by Kinins and Products of Similar Converting-Enzyme Systems: Enalapril attenuates endothelin-1-induced hypertension via increased kinin survival

1 Department of Pharmacology and Toxicology, Vascular Biology Center, Medical College of Georgia, Augusta, Georgia 30912; and 2 The Second Swedish National Pension Fund AP2, Gothenburg, Sweden SE-40424 Recent studies have shown that angiotensin-converting enzyme (ACE) inhibitors attenuate endothelin-1 (ET-1)-induced hypertension, but the mechanisms for this effect have not been clarified. Initial experiments were conducted to contrast the effect of the ACE inhibitor enalapril, the combined ACE-neutral endopeptidase inhibitor omapatrilat, and the angiotensin II receptor antagonist candesartan on the hypertensive and renal response to ET-1 in anesthetized Sprague-Dawley rats. Acute intravenous infusion of ET-1 (10 pmol · kg 1 · min 1 ) for 60 min significantly increased mean arterial pressure (MAP) from 125 ± 8 to 145 ± 8 mmHg ( P