ANTIHYPERTENSIVE MECHANISM OF ALACEPRIL - EFFECT ON NOREPINEPHRINE-INDUCED VASOCONSTRICTIVE RESPONSE INVITRO AND INVIVO

  • 1 January 1986
    • journal article
    • research article
    • Vol. 36-1  (1) , 74-77
Abstract
To investigate the antihypertensive mechanism of 1-[(S)-3-acetylthio-2-methylpropanoyl]-L-prolyl-L-phenylalanine (alacepril, DU-1219) a novel orally active angiotensin converting enzyme inhibitor, we studied the inhibitory activity of alacepril and DU-1227 (desacetyl-alacepril, a metabolite of alacepril) on the norepinephrine (noradrenaline, NA)-induced vasoconstrictive and pressor response in vitro and in vivo, and compared with that of captopril. Alacepril and captopril (3 .times. 10-4 mol/l) attenuated slightly the NA-induced contractile response in isolated rat thoracic aorta and mesenteric artery, however, DU-1227 (3 .times. 10-4 mol/l) inhibited more strongly the response in main artery and peripheral vascular bed. Orally given alacepril (18.7 mg/kg) inhibited the NA-induced pressor response in conscious normotensive rats, and the activity was more potent and long-lasting than that of an equimolar dose of captopril (10 mg/kg). After oral administration in hypertensive rats challenged with NA, alacepril (1.87 to 18.7 mg/kg) showed a dose-related antihypertensive effect which was slower in onset and longer lasting than that of equimolar dose of captopril (1.0 to 10.0 mg/kg). Consequently, the reduced sensitivity of the sympathetic nervous system in peripheral vasculature might contribute partly to the antihypertensive mechanism of alacepril.