Effect of angiotensin-converting enzyme inhibition on circulating and local kinin levels.
Angiotensin-converting enzyme kininase II reduces bradykinin metabolism in vitro and in vivo. However, consistent changes in circulating bradykinin levels after the angiotensin-converting enzyme inhibitor captopril have not been reported. The kallikrein-kinin system has been suggested to be a local hormonal system concerned with regional blood flow, and hence circulating levels may not reflect local tissue levels of kinins. Anesthetized dogs given captopril had a significant increase in urinary kinin excretion without a change in circulating bradykinin levels or in urinary kallikrein. These changes in renal kinins were accompanied by a decrease in blood pressure and renal vasodilation. The hypotension and renal vasodilation produced by captopril were not attenuated either by pretreatment with the angiotension receptor antagonist Sar1-Ileu8-angiotensin II or by reduction of endogenous prostaglandin production with indomethacin. Postischemic renal vasodilation after temporary renal artery occlusion was also associated with increased urinary kinin levels. These results demonstrate that captopril effectively inhibits renal angiotensin-converting enzyme and that the renal kallikrein-kinin system may play an important role in regulating the renal vasculature and may contribute to the renal hemodynamic effects of captopril. Many polypeptide hormone membrane receptors are self-regulated by endogenous tissue concentrations of the peptide hormone. Infusions of bradykinin into rats reduced specific bradykinin receptors. A similar decrease in bradykinin receptor numbers without change in receptor affinity was demonstrated after captopril administration. These results provide indirect evidence that angiotensin-converting enzyme/kininase inhibition by captopril increases local tissue concentration of kinins, which may contribute to the hypotensive effect.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001920:Bradykinin / Q000378:metabolism; D002216:Captopril / Q000494:pharmacology; D004285:Dogs; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007610:Kallikreins / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007705:Kinins / Q000378:metabolism*; D051381:Rats; D018002:Receptors, Bradykinin; D011956:Receptors, Cell Surface / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D007705:Kinins; D018002:Receptors, Bradykinin; D011956:Receptors, Cell Surface; D002216:Captopril; D007610:Kallikreins; D001920:Bradykinin