EFFECT OF BRADYKININ ON PERIPHERAL ARTERIES AND VEINS IN MAN

ACE inhibitors develop most of their effects by inhibition of the renin-angiotensin system. But as we know today, ACE inhibitors interact with many other local or systemic hormone systems of which the kinins play the most relevant role. Angiotensin-I converting enzyme is identical with the kininase II of the kallikrein-kinin systems and its inhibition leads to a potent stimulation of kinins. In our studies now we investigated the vascular effects of kinins in normotensive volunteers before and after ACE inhibition by 50 mg of captopril. Bradykinin diminished systemic blood pressure in a dose dependent manner by reduction of peripheral vascular resistance in consequence of direct vasodilation. This effect appears to be independent of prostaglandins, since inhibition of prostaglandin synthesis by 100 mg of indomethacin had no effect on the blood pressure lowering effect of bradykinin. ACE inhibition potentiated the kinin effect about 20- to 50-fold. Tone of dorsal hand veins could be increased by noradrenalin. Bradykinin was able to decrease dorsal hand vein tone markedly after precontraction by noradrenalin. The effect was dose-related. However, if compared to the effect in the arteries its time course was clearly prolonged, i.e. the onset was observed first after one minute of infusion (in arteries after seconds) and the maximun was reached after 4 minutes. Our results show that bradykinin dilates in vivo arteries as well as dorsal hand veins in a dose-dependent manner and that ACE inhibition potentiates these kinin 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 underlying mechanisms, however, were not clarified finally. Our results now suggest that potentiation of endogenous kinins might play an important role in these hemodanamic effects of ACE inhibitors.