Contrasting effects of No on food intake and Gh secretion stimulated by a Gh releasing peptides (GHRP) in youg 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. Methods, In the food-intake experiments, adult Sprague-Dawley male rats underwent acute administration of: 1) EP92632 (160 ~g/kg , sc): 2) molsidomine (100mg/kg, ip): 3) EP92632+ molsidomine; 4) L-NAME (60mg/kg, ip); 5) EP92632 + L-NAME (60mg/kg, ip): 6) EP92632+ molsidomine+L-NAME (60mg/kg, ip): 7)0.9%saline(0.1ml/kg, ip). Inthe neuroendocrine experiments, rats were given the same cempounds accerding to the above reported schedule, except for the use of a lower EP92632 dose (80 ~ g/kg, sc). Results. EP92632 significantly stimulated food-intake (3A±0.6 vs. 2,6±0.7g, P<0.01), an effect which was further enhanced by molsidomine (6.4±0.6g. P<O.O1), 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 (AUC<GH (}'90:18617,9±2267.8 ng/ml/min vs. 10267 ,1±1445.6 ng/ml/min, P<0.01), but, in centrast to the food-intake experiments, molsidomine significantly inhibited both basal and EP9263 2-stimulated GH secretion (at 10,15 and 30min and at 30min, respectively , P<0 .01 vs. saline+saline); 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 (AUC'GH0.90: 4307.8±688.1 ng/ml/min; P<0.01 vs. saline+saline; AUC'GH 0.90: 14032.3±1828.3 ng/mllmin; P<0.01 vs. saline+EP92632; respectively). Conclusions. These data indicate that NO in the rat stimulates the GHRP-mediated effect on food-intake, but exerts a dual action, likely stimulatory at hypothalamic and inhibitory at pituitary levels , on basal and GHRPs-stimulated GH secretion