Angiotensin-converting enzyme inhibition and prostaglandins.
To determine whether prostaglandins contribute to the depressor response of angiotensin-converting enzyme inhibitors, plasma prostaglandin levels were measured by radioimmunoassay in normo- and hypertensive subjects on both sodium-restricted and sodium-loaded diets before and after captopril administration. On the sodium-restricted diet, the hypotensive response to captopril was accompanied by significant increments in the metabolite of prostaglandin E2 (PGE2-M) and bradykinin and by significant decrements in angiotensin II. The high sodium diet suppressed the response of the renin-angiotensin and kinin systems to captopril but the hypotensive response persisted. Furthermore, the decrease in blood pressure correlated significantly with increments in prostaglandin E2-metabolite. Prostaglandin synthesis was then inhibited in the sodium-restricted hypertensive patients by pretreatment with indomethacin. This maneuver completely eliminated the captopril-induced prostaglandin E2-metabolite increment without changing bradykinin or angiotensin II responses but significantly attenuating the hypotensive response. Finally, when patients were studied on a high sodium intake, similar effects were observed except now indomethacin completely abolished the blood pressure response to captopril. These studies therefore support the hypothesis that increased production of vasodilator prostaglandins in a major mediator of the hypotensive response to captopril. Whether the change in prostaglandin release is a direct effect of the drug or secondary to increased kinin levels is uncertain.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood*; D000806:Angiotensin-Converting Enzyme Inhibitors; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000627:therapeutic use; D004039:Diet, Sodium-Restricted; D015232:Dinoprostone / Q000031:analogs & derivatives; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology*; D007213:Indomethacin / Q000627:therapeutic use; D011292:Premedication; D011458:Prostaglandins E / Q000097:blood*; D012084:Renin-Angiotensin System / Q000187:drug effects; D014882:Water-Electrolyte Balance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D011458:Prostaglandins E; C025087:15-keto-13,14-dihydroprostaglandin E2; D015121:6-Ketoprostaglandin F1 alpha; D002216:Captopril; D015232:Dinoprostone; D007213:Indomethacin