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 NG-monomethyl-L-arginine (L-NMMA) and NG-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 micrograms . 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.
Vozzo
R
R
University of Adelaide, Department of Medicine, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia, Australia 5000.
Wittert
G A
GA
Horowitz
M
M
Morley
J E
JE
Chapman
I M
IM
D000293:Adolescent; D000328:Adult; D001066:Appetite / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004435:Eating / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006815:Hunger / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D012528:Satiety Response / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester