EFFECT OF BRADYKININ ON PERIPHERAL ARTERI ES AND VEINS IN MAN

ACE inhibitors develop most of their effects by inhibition of the reni n-angiotensin system. But as we know today, ACE inhibitors interact wi th many other local or systemic hormone systems of which the kinins pl ay the most relevant role. Angiotensin-I converting enzyme is identica l with the kininase II of the kallikrein-kinin systems and its inhibit ion leads to a potent stimulation of kinins. In our studies now we inv estigated the vascular effects of kinins in normotensive volunteers be fore and after ACE inhibition by 50 mg of captopril. Bradykinin dimini shed systemic blood pressure in a dose dependent manner by reduction o f peripheral vascular resistance in consequence of direct vasodilation . This effect appears to be independent of prostaglandins, since inhib ition of prostaglandin synthesis by 100 mg of indomethacin had no effe ct on the blood pressure lowering effect of bradykinin. ACE inhibition potentiated the kinin effect about 20- to 50-fold. Tone of dorsal han d veins could be increased by noradrenalin. Bradykinin was able to dec rease dorsal hand vein tone markedly after precontraction by noradrena lin. The effect was dose-related. However, if compared to the effect i n the arteries its time course was clearly prolonged, i.e. the onset w as observed first after one minute of infusion (in arteries after seco nds) and the maximun was reached after 4 minutes. Our results show tha t bradykinin dilates in vivo arteries as well as dorsal hand veins in a dose-dependent manner and that ACE inhibition potentiates these kini n effects markedly. Changes in hemodynamic parameters raised in recent clinical studies after ACE inhibition showed that ACE inhibitors are able to diminish the cardiac pre- and after-load simultaneously. The u nderlying mechanisms, however, were not clarified finally. Our results now suggest that potentiation of endogenous kinins might play an impo rtant role in these hemodanamic effects of ACE inhibitors.