Contrasting effects of nitric oxide on food intake and GH secretion stimulated by a GH-releasing peptide

Objective: Among the many actions of nitric oxide (NO) are those on endocri ne and feeding behaviour. Based on NO involvement in the GH-releasing effec t of the CH-releasing peptides (GHRPs) and the reported orexigenic activity of these compounds, we sought to evaluate the effect of the combined admin istration of a long-acting NO donor, molsidomine, and the newly synthesized GHRP EP92632 on food intake and GH secretion in rats. Moreover, to verify the specificity of a potential NO involvement, we evaluated whether or not the effects of GHRPs were abolished by a pre-treatment with an inhibitor of NO synthase, N-nitro-arginine-methyl-ester (NAME). Methods: In the food intake experiments, adult Sprague-Dawley male rats und erwent acute administration of: (1) EP92632 (160 mug/kg. s.c.): (2) molsido mine (100 mg/kg, i.p.); (3) EP92632+molsidomine: (4) L-NAME (40 and 60 mg/k g, i.p,): (5) EP92632+L-NAME (60 mg/kg, i.p.): (6) EP92632+molsidomine+L-NA ME (60 mg/kg, i.p.): and (7) 0.9%, saline (0.1 ml/kg, i.p.). After treatmen ts, the cumulative food intake in the 6 post-treatment hours was carefully evaluated. In the neuroendocrine experiments, rats were given the same comp ounds according to the above reported schedule, except for the use of one d ose of NAME (60 mg/kg, i.p.) and a lower EP92632 dose (80 mug/kg. s.c.), an d were sampled via atrial cannula. Results: EP92632 significantly stimulated food intake, an effect which was further enhanced by molsidomine, though the latter did not elicit per se an y orexigenic effect. L-NAME given alone significantly decreased food intake and abolished the orexigenic effect of the GHRP and the enhancing effect o f molsidomine. Plasma GH levels increased significantly following administr ation of EP92632 but, in contrast to the food intake experiments, molsidomi ne significantly inhibited both basal and EP92632-stimulated GH secretion: moreover, NAME had a biphasic effect on the EP92632-stimulated GH release: initially inhibitory and then, from 45 min on, stimulatory. NAME did not af fect basal GH levels but, surprisingly, combined administration of molsidom ine and NAME induced a striking inhibition of both basal and the peptide-st imulated GH release. Conclusions: In summary. these data indicate that NO in the rat is physiolo gically involved in a stimulatory way in the GHRP-mediated effect on food i ntake, but exerts a dual action, probably stimulatory at hypothalamic and i nhibitory at pituitary levels, on basal and GHRP-stimulated CH secretion.