Effects of converting-enzyme inhibitors on the renin-angiotensin-aldosterone, bradykinin, and arachidonic acid-prostaglandin systems: correlation of chemical structure and biologic activity.
The renin-angiotensin-aldosterone system plays an integral role in the control of BP and is mediated by enzymatic transformation of substances in the renin-angiotensin cascade. Inhibitors of various reactions in this cascade have been shown experimentally to reduce elevated BP. The first such compound to become available for clinical use was the angiotensin-converting enzyme inhibitor captopril. Captopril reduces BP, with the expected decrease in plasma angiotensin II concentration and increases in renin and angiotensin I levels, but there is also evidence for a non-renin-dependent mechanism of action. In particular, according to cell culture data, captopril stimulates an increase in the synthesis of vasodilatory prostaglandins. Because enalapril, another angiotensin-converting-enzyme inhibitor, does not augment in vitro synthesis of prostaglandins, this effect may be unique to the chemical structure of captopril rather than inherent to all such inhibitors. Studies using animal models of hypertension support this hypothesis. Captopril may also influence prostaglandin synthesis by reducing inactivation of bradykinin.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000502:physiology*; D002216:Captopril / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology; D006801:Humans; D011453:Prostaglandins / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000806:Angiotensin-Converting Enzyme Inhibitors; D001095:Arachidonic Acids; D011453:Prostaglandins; D016718:Arachidonic Acid; D004656:Enalapril; D002216:Captopril; D001920:Bradykinin