Effect of nitric oxide synthase inhibitors on short-term appetite and food intake in humans

Animal studies suggest that nitric oxide (NO) may be a physiological regulator of appetite; NO synthase (NOS) inhibition suppresses food intake in rats, mice, and chickens. It is not known whether NO has any effect on appetite in humans. We have used N-G-monomethyl-L-arginine (L-NMMA) and N-G-nitro-L-arginine methyl ester (L-NAME), both competitive, nonselective inhibitors of NOS, in two separate studies to evaluate the role of NO in the short-term regulation of appetite in humans. In study I, 13 men (18-25 yr) underwent paired studies, in randomized, double-blind fashion, after an overnight fast. L-NMMA (4 mg.kg(-1).h(-1)) or saline (0.9%) was infused intravenously at a rate of 40 ml/h for 1.5 h. In study II, eight men (18-26 yr) underwent three randomized, double-blind studies after an overnight fast. L-NAME (75 or 180 mu g.kg(-1).h(-1))or saline (0.9%) was infused intravenously at a rate of 20 ml/h for 120 min. Hunger and fullness were measured using visual analog scales; blood pressure and heart rate were monitored, and 30 min before the end of the infusion, subjects were offered a cold buffet meal. Total caloric intake and the macronutrient composition of the meal were determined. Both L-NMMA (P = 0.052) and L-NAME (P < 0.05; both doses) decreased heart rate, L-NMMA increased diastolic blood pressure (P < 0.01), and L-NAME increased systolic blood pressure (P = 0.052). Neither drug had any effect on caloric intake or sensations of hunger or fullness. Despite having significant effects on cardiovascular function in the doses used, neither L-NMMA nor L-NAME had any effect on feeding, suggesting that NO does not affect short-term appetite or food intake in humans.