INFLUENCE OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITION ON SYMPATHETIC NEUROTRANSMISSION - POSSIBLE ROLES OF BRADYKININ AND PROSTAGLANDINS

Effects of angiotensin-converting enzyme (ACE) inhibitors on sympathetic neurotransmission have generally been ascribed to their ability to block angiotensin II (Ang II) formation, but they also inhibit the degradation of vasoactive kinins, such as bradykinin. The latter may, in turn, lead to enhanced prostaglandin formation. Prostaglandlins have been reported to influence sympathetic neurotransmission at different sites; much less is known about the influence of bradykinin due to the lack (until recently) of specific and effective bradykinin receptor antagonists, and difficulties with measurements of true plasma or tissue levels of bradykinin. Bradykinin may modulate sympathetic activity via a central stimulatory action and via activation of sensory input to the central nervous system; however, the importance of bradykinin for central effects of ACE inhibition remain to be established. At the sympathetic neuro-effector junction, results are more conflicting. Thus, bradykinin has been reported to enhance or reduce peripheral noradrenergic transmission or even lack any effect. Possible explanations for the differing results obtained include species and/or tissue differences in the responses to bradykinin. Also, the effects of bradykinin may be influenced by enhanced formation of prostaglandins and/or endothelium-derived relaxing factor (EDRF), which may contribute to the confusion. As most studies have been performed under in vitro conditions and with high doses of bradykinin, the physiological relevance of the data may be questioned. Hence, the importance of bradykinin-related mechanisms must be confirmed with physiologically sound experiments and by the use of specific bradykinin receptor antagonists, which will establish whether or not the endogenous levels of bradykinin under basal conditions or during ACE inhibition are of importance for interactions with sympathetic neurotransmission. In canine skeletal muscle in situ we have shown that reduced Ang II production, enhanced bradykinin accumulation, and augmented formation of prostaglandins all seem to contribute to the effect of ACE inhibition on sympathetic vascular neuro-effector mechanisms.