Effect of alacepril on renin-angiotensin-aldosterone system and kallikrein-kinin-prostaglandin system in experimental animals.
The effects of 1-[(S)-3-acetylthio-2-methylpropanoyl]-L-prolyl-L-phenylalanine (alacepril, DU-1219), an orally active angiotensin converting enzyme (ACE) inhibitor, on humoral factors which participated in the blood pressure control were examined with various experimental animals. In conscious renal hypertensive dogs, alacepril (3 mg/kg p.o.) showed decreases in plasma ACE activity and plasma aldosterone concentration, and increases in plasma renin activity and plasma angiotensin I concentration accompanied by a significant reduction in blood pressure. In conscious normotensive dogs, alacepril (1 and 3 mg/kg p.o.) showed an increase in urinary excretion of bradykinin accompanied by increases in urinary water and sodium excretion. In spontaneously hypertensive rats, alacepril (30 and 100 mg/kg p.o.) showed increases in urinary excretion of bradykinin and 6-keto-prostaglandin Fl alpha, and a decrease in that of aldosterone accompanied by increased in excretion of water and sodium. These results indicate that the antihypertensive activity of alacepril is due to the suppression of renin-angiotensin-aldosterone system and the enhancement of kallikrein-kinin-prostaglandin system through the inhibition of ACE (kininase II) activity in vivo.
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000450:Aldosterone / Q000097:blood / Q000652:urine; D000803:Angiotensin I / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000652:urine*; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology; D015232:Dinoprostone; D004285:Dogs; D006973:Hypertension / Q000503:physiopathology; D006978:Hypertension, Renovascular / Q000503:physiopathology; D007610:Kallikreins / Q000652:urine*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011453:Prostaglandins / Q000652:urine*; D011458:Prostaglandins E / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR; D012084:Renin-Angiotensin System / Q000187:drug effects*; D014882:Water-Electrolyte Balance / Q000187:drug effects
D000959:Antihypertensive Agents; D011453:Prostaglandins; D011458:Prostaglandins E; D000450:Aldosterone; D015121:6-Ketoprostaglandin F1 alpha; D000803:Angiotensin I; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D007610:Kallikreins; D015232:Dinoprostone; D001920:Bradykinin; C046835:alacepril