Human leptin stimulates systemic nitric oxide production in the rat.
OBJECTIVE
Apart from having an effect on energy balance, leptin is also involved in cardiovascular regulation and in the pathogenesis of obesity-associated hypertension. We investigated the effect of leptin on nitric oxide (NO) production.


METHODS
Wistar rats were placed in metabolic cages, and urine was collected in 2-hour periods. After the control period, leptin (1 mg/kg intraperitoneal) was administered, and urine collection was continued for up to 6 hours. Blood was obtained 0.5, 1, 2, 4, and 6 hours after hormone injection.


RESULTS
Leptin increased plasma concentrations of NO metabolites (nitrates + nitrites, NO(x)) by 32.5%, 58.0%, and 29.7% at 1, 2, and 4 hours, respectively. Urinary NO(x) excretion increased by 28.8% in the first and by 20.1% in the second 2-hour period after injection. The plasma concentration of the NO second messenger, cyclic guanosine 3',5'-monophosphate (cGMP), increased by 83% and 50.6% at 2 and 4 hours after leptin administration, respectively. Urinary excretion of cyclic GMP increased by 36.1% in the first and by 43.1% in the second 2-hour period. Leptin had no effect on the plasma concentration of atrial natriuretic peptide (ANP). The effect of leptin on plasma and urinary NO(x) was abolished by the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) (30 mg/kg intraperitoneal) administered 15 minutes before leptin injection. L-NAME alone caused a 32.2% increase in systolic blood pressure, but this increase was not observed in rats receiving L-NAME and leptin.


CONCLUSIONS
The results indicate that leptin stimulates systemic NO production; leptin prevents blood pressure elevation induced by acute NO blockade, suggesting that leptin also triggers additional hypotensive mechanisms; and ANP is not involved in renal and vascular effects of leptin.
Beltowski
Jerzy
J
Department of Pathophysiology, Medical University, ul. Jaczewskiego 8, 20-090 Lublin, Poland. patfiz@asklepios.am.lublin.pl
Wójcicka
Grazyna
G
Borkowska
Ewa
E
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000097:blood / Q000652:urine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood / Q000652:urine; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000097:blood / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology
D004791:Enzyme Inhibitors; D020738:Leptin; D009566:Nitrates; D009573:Nitrites; D011994:Recombinant Proteins; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester