ROLE OF NITRIC-OXIDE AND CYCLIC-GMP AS MEDIATORS OF ENDOTHELIUM-INDEPENDENT NEUROGENIC RELAXATION IN BOVINE MESENTERIC-ARTERY

Electrical field stimulation (EFS) of phenylephrine-contracted bovine mesenteric ateries pretreated with guanethidine elicited a relaxation that amounted to roughly 40%. This relaxation was sensitive to tetrodotoxin pretreatment, suggesting a neurogenic origin. The EFS-induced relaxation was correlated to an increase in cGMP level, from 14.2 +/- 2.5 pmol/g wet wt in nonstimulated arteries to 31.6 +/- 3.4 pmol/g wet wt after 1 minute of EFS. cAMP values were not affected by EFS. Methylene blue (5-mu-M) and the compound LY 83583 (10-mu-M), inhibitors of soluble guanylate cyclase, inhibited the EFS-induced relaxation by 60% and 50%, respectively. Zaprinast (1-mu-M), a selective inhibitor of cGMP degradation, significantly (p = 0.005) potentiated the EFS-induced relaxation. The relaxation induced by EFS in bovine mesenteric arteries exhibits characteristics similar to the relaxation evoked by organic nitroesters and endothelium-dependent vasodilators, both of which are suggested to be mediated by cGMP and probably with nitric oxide as the common activator of the cGMP system. The possible involvement of nitric oxide as a mediator of EFS-induced relaxations was investigated with the use of known modulators of endogenous nitric oxide production. Preincubation of the arteries with 1 mM arginine or 1 mM N-alpha-benzoyl-L-arginine, both reported to potentiate endogenous nitric oxide production, or 5 mM L-canavanine, 0.25 mM N(G)-monomethyl-L-arginine, or 0.1 mM N(G)-nitro-L-arginine, alleged inhibitors of endogenous nitric oxide production, were without effect on the relaxation induced by EFS. However, pyrogallol, a generator of superoxide anions, was a potent inhibitor of relaxations induced by EFS in bovine mesenteric arteries. These results suggest the existence of a neurogenic and cGMP-mediated relaxation in bovine mesenteric arteries, and also suggest that nitric oxide may participate in this signal transduction, although no evidence for an involvement of the L-arginine pathway in the generation of nitric oxide could be found.