Contrasting effects of NO on food intake and GH secretion stimulated by a GH releasing peptide (GHRP) in rats

Objective. Based on NO involvement in the GH-releasing effect of the GH-releasing peptides (GHRP s) and the reported orexigenic activity of these compounds, we sought to evaluate the effect of the combined administration of a long-acting NO-donor, molsidomine, and/or an inhibitor of NO-synthase, N-nitro-arginine-methyl-ester (NAME). and the GHRP EP92632 on food-intake and GH secretion in rats. Results. EP92632 significantly stimulated food-intake an effect which was further enhanced by molsidomine which had no orexigenic effect per se. L-NAME significantly decreased food-intake and abolished the orexigenic effect of the GHRP and the enhancing effect of molsidomine. Plasma GH levels increase d significantly following admi nistration of EP92632 but, in centrast to the food-intake experiments, molsidomine significantly inhibited both basal and EP9263 2-stimulated GH secretion ; moreover, NAME exerted a biphasic effect on the EP92632-stimulated GH release, being, initially, inhibitory and, then, from 4Smin on, stimulatory. NAME did not affect basal GH levels but surprisingly, combined administration of molsidomine and NAME induced a striking inhibition of both basal and the peptide-stimulated GH release. Conclusions. These data indicate that NO in the rat stimulates the GHRP-mediated effect on food-intake, but exerts a dual action, likelystimulatory at hypothalamic and inhibitory at pituitary levels , on basaland GHRPs-stimulated GH secreti on.