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 -monomethyl-l-arginine (l-NMMA) and N -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 ⋅ h ) 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 μg ⋅ kg ⋅ h ) 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) andl-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, neitherl-NMMA norl-NAME had any effect on feeding, suggesting that NO does not affect short-term appetite or food intake in humans.