Abstract-The potentiation of kinin actions represents a cardioprotective property of ACE inhibitors. Although a clear contribution to this effect is related to the inhibition of bradykinin (BK) breakdown, the high efficacy of potentiation and the ability of ACE inhibitors to provoke a B 2 -receptor-mediated response even after receptor desensitization has also triggered hypotheses concerning additional mechanisms of kinin potentiation. The application of kinin analogues with enhanced metabolic stability for the demonstration of degradation-independent mechanisms of potentiation, however, has yielded inconsistent results. Therefore, the relation between the susceptibility of B 2 -agonists to ACE and the potentiation of their actions by ACE inhibitors was investigated with the use of minimally modified kinin derivatives that varied in their degree of ACE resistance. ]-BK were both significantly potentiated by a factor of 4.4, whereas the activities of the other agonists were not affected. Ramiprilat exerted no influence on the maximum contraction induced by any of the agonists. It is concluded that the potentiation of kinin analogues during ACE inhibition correlates quantitatively with the susceptibility of each substance to degradation by ACE. As such, no evidence of degradation-independent potentiating actions of ACE inhibitors could be obtained. Key Words: bradykinin Ⅲ angiotensin-converting enzyme Ⅲ receptors, bradykinin Ⅲ kinins Ⅲ rabbits P otentiation of kinin actions is a well-known property of angiotensin I-converting enzyme inhibitors, an effect attributed to a protection of kinins against ACE enzymatic degradation. This mechanism contributes to the therapeutic spectrum of ACE inhibitors in vivo. A variety of experimental studies have demonstrated that enhancement of kinin effectiveness is responsible for beneficial influences of ACE inhibitors on the cardiovascular system, such as reduction of infarct size, inhibition of myocardial hypertrophy and fibrosis, and protection against the development of hypertension (reviewed by Linz et al 1 ). The contribution of endogenous kinins to the vasodilatory effect of an ACE inhibitor has recently been demonstrated in humans as well. 2 Such kininmediated effects can arise because of the high extent to which ACE inhibitors potentiate the effectiveness of kinins. In volunteers, ACE inhibitor treatment sensitized the blood pressure response to injected bradykinin (BK) by a factor of Ϸ40. 3 However, attempts to correlate this intriguing effect with BK accumulation have failed because (1) plasma kinin levels increase only modestly after ACE inhibition, 4 and (2) kinin potentiation by ACE inhibitors is also observed in experimental models in which kinin degradation should be negligible (eg, in superfused vessels 5 ).This fact, and the observation that after desensitization by prolonged kinin exposure an ACE inhibitor can reestablish a B 2 -receptor-mediated response in the continued presence of the desensitizing kinin concentration (a phenomenon addressed as "receptor re...

No abstract