Human Leptin Stimulates Systemic Nitric Oxide Production in the Rat

Abstract

BELTOWSKI, JERZY, GRAŻ YNA WÓ JCICKA, AND EWA BORKOWSKA. Human leptin stimulates systemic nitric oxide production in the rat. Obes Res. 2002;10: 939 -946. 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. Research Methods and Procedures: 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 ϩ 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 3Ј,5Ј-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. Discussion: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.

Adiponectin, leptin, nitric oxide, and C-reactive protein levels in kidney transplant recipients: comparison with the hemodialysis and chronic renal failure

“…12 At the molecular level, the effect of leptin on endothelial function is unclear as leptin both stimulates the activity of endothelial nitric oxide synthase (eNOS) and reduces the bioavailability of L-arginine required for NO synthesis. 17,18 However, in another study, leptin promoted NO production, thereby generating antiatherogenic effects. 19 Ku et al 20 and…”

The Effect of L-NAME Treatment on Leptin Associated Retinal Nitrosylation in Hypercarbic Oxygen Induced Retinopathy in Newborn Rats

“…12 NO me di a ted da ma ge of lep tin is sug ges ted to be in hi bi ted by L-NA ME ad mi nis tra ti on. 7,18,19,23 The high pro duc ti on ra te of ox gen ra di cals and pe roxy nit ri te will le ad to the fa i lu re of an ti o xi da tive ca pa city, and the pro te in at tack of pe roxy nit rite pro du ces pro te in tyro si ne nit ra ti on. 28 Nit rot yro si ne is a bi o mar ker of re ac ti ve nit ro gen spe ci es and an in di ca tor of pe roxy nit ri te for ma tion.…”

“…Lep tin sti mu la tes NO pro duc ti on in en dot he li al cells by in te rac ting with its re cep tor on the cell mem bra ne. [18][19][20][21] Stu di es al so in di ca ted that lep tin sig ni fi cantly in cre a sed in tracel lu lar re ac ti ve oxy gen ra di cal for ma ti on in endot he li al cells and ca u sed en dot he li al da ma ge thro ugh oxi da ti ve stress. [22][23][24] Un der the exis ten ce of in cre a sed ox yra di cals, nit ric oxi de un der go es a rapid re ac ti on with su pe ro xi de ra di cals to form pe roxy nit ri te, which may be anot her me di a tor of oxi da ti ve stress.…”

Regulatable atrial natriuretic peptide gene therapy for hypertension

“…Measurement of urinary cGMP output serves as an accurate, noninvasive means of monitoring the bioactivity of plasma ANP (18). To take advantage of this fact, the mice used above to investigate long-term, Mfp-inducible ANP expression were used simultaneously to investigate the bioactivity of Mfp-inducible ANP.…”