Cyclic GMP Modulates Release of Norepinephrine From Adrenergic Nerves Innervating Canine Arteries

Abstract

Evidence is presented that compounds which stim-ulate the soluble form of the enzyme guanylate cy-clase or which inhibit the enzyme cGMP phospho-diesterase (PDE), responsible for the degradation of cGMP (including endothelium-derived relaxing factor) are inhibitors of sympathetic neurotransmis-sion to vascular smooth muscle and inhibit the ef-flux of norepinephrine from sympathetic nerves. Moreover, prostacyclin, papaverine, iloprost, and forskolin, compounds which stimulate the enzyme adenylate cyclase, and rolipram (neural specific) and milrinone, enoximone, and piroximone (muscle specific) inhibitors of Type III cAMP PDE and degradation of cAMP, do not inhibit nerve stimulation to most blood vessels. The data support the concept that cGMP may act as a negative feedback modulator of physiologic frequencies of sympathetic nerve activity to blood vessels. cAMP does not appear to modulate adrenergic neurotransmission to vascular smooth muscle at physiologic frequencies of neural stimulation. Am J Hypertens 1991;4:173–176