Endothelium-Derived and Intraneuronal Nitric Oxide-Dependent Inhibition of Norepinephrine Efflux From Sympathetic Nerves by Bradykinin

Evidence is presented that bradykinin inhibits norepinephrine efflux from sympathetic nerves innervating canine mesenteric and pulmonary arteries, in part, by releasing endothelium-derived relaxing factor (EDRF) from the vascular endothelium. Moreover, in the absence of vascular endothelium, bradykinin also inhibits norepinephrine efflux from the sympathetic nerve terminals innervating these blood vessels. This inhibition is attenuated by canavanine and LNMMA, which inhibit the conversion of arginine to nitric oxide, and is enhanced after overnight incubation of blood vessels with arginine. In endothelium-rubbed blood vessels the inhibitory effect of bradykinin on norepinephrine efflux is enhanced by increasing extracellular calcium ion (Ca2+o) and attenuated by nitrendipine. We propose that bradykinin inhibits norepinephrine efflux by stimulating intraneuronal nitric oxide from arginine.