Interneuronal Cyclic GMP and ‘EDRF-like Substance’ Modulate Norepinephrine Release from Peripheral Sympathetic Nerves

ABSTRACT Stimulators of cyclic 3′5′ guanosine monophosphate (cGMP) or release of endothelium-derived relaxing factor (EDRF) inhibit sympathetic neurotransmission (SNS) to canine mesenteric (MA) and porcine carotid arteries (CA). Inhibitors of guanylate cyclase and 1-N-monomethylarginine (LNMMA) enhance contractions to SNS and the calcium-dependent efflux of 2- 14 C-norepinephrine (NE). In endotheliumdamaged porcine CA the responses to SNS, but not NE, are enhanced by LNMMA and inhibited by difluoromethylornithine (DFMO) an inhibitor of ornithine decarboxylase which shunts ornithine into endogenous arginine via citrulline. Thus, intraneuronal EDRF-like substance and cyclic GMP may act as endogenous inhibitory feedback modulators of calcium-dependent release of sympathetic neurotransmitter in vascular smooth muscle.