Role of bradykinin in the cardiac effects of angiotensin-converting enzyme inhibitors.
Angiotensin-converting enzyme (ACE) inhibitors exert their beneficial effects not only via endocrine mechanisms, but most probably also via interference with autocrine-paracrine actions involving local renin-angiotensin and kallikrein-kinin systems with subsequent autacoid release. Inhibition of ACE (kininase II) results in the reduction of angiotensin II generation and kinin degradation, leading to beneficial cardiovascular effects. Bradykinin and prostacyclin release from isolated rat hearts was increased by local ACE inhibitions with ramiprilat. In different models the bradykinin-mediated effects of ACE inhibition were abolished with the specific B2 kinin-receptor antagonist Hoe 140: The cardioprotective effects of ramiprilat or ramipril such as reduction of postischemic reperfusion injuries in isolated rat hearts or the reduction in infarct size in dogs and rabbits were abolished by coadministration of Hoe 140. Furthermore, left ventricular hypertrophy in rats with aortic banding could be prevented or regression was induced when the ACE inhibitor was given in a non-blood pressure-lowering dose. These beneficial effects were also abolished by Hoe 140. In conclusion, in different experimental models, ACE inhibitors exert cardioprotective effects. An enhancement of endothelial autacoid formation (nitric oxide and prostacyclin) by inhibiting degradation of bradykinin may contribute to these effects.
D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D006332:Cardiomegaly / Q000503:physiopathology; D011464:Epoprostenol / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D016234:Kallikrein-Kinin System / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*; D015427:Reperfusion Injury / Q000503:physiopathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D009569:Nitric Oxide; C065679:icatibant; D011464:Epoprostenol; D001920:Bradykinin