Leptin-induced endothelium-dependent vasorelaxation of peripheral arteries in lean and obese rats: role of nitric oxide and hydrogen sulfide.

Abstract

Adipose tissue hormone leptin induces endothelium-dependent vasorelaxation mediated by nitric oxide (NO) and endothelium-derived hyperpolarizing factors (EDHF). Previously it has been demonstrated that in short-term obesity the NO-dependent and the EDHF-dependent components of vascular effect of leptin are impaired and up-regulated, respectively. Herein we examined the mechanism of the EDHF-dependent vasodilatory effect of leptin and tested the hypothesis that alterations of acute vascular effects of leptin in obesity are accounted for by chronic hyperleptinemia. The study was performed in 5 groups of rats: (1) control, (2) treated with exogenous leptin for 1 week to induce hyperleptinemia, (3) obese, fed highly-palatable diet for 4 weeks, (4) obese treated with pegylated superactive rat leptin receptor antagonist (PEG-SRLA) for 1 week, (5) fed standard chow and treated with PEG-SRLA. Acute effect of leptin on isometric tension of mesenteric artery segments was measured ex vivo. Leptin relaxed phenylephrine-preconstricted vascular segments in NO- and EDHF-dependent manner. The NO-dependent component was impaired and the EDHF-dependent component was increased in the leptin-treated and obese groups and in the latter group both these effects were abolished by PEG-SRLA. The EDHF-dependent vasodilatory effect of leptin was blocked by either the inhibitor of cystathionine γ-lyase, propargylglycine, or a hydrogen sulfide (H2S) scavenger, bismuth (III) subsalicylate. The results indicate that NO deficiency is compensated by the up-regulation of EDHF in obese rats and both effects are accounted for by chronic hyperleptinemia. The EDHF-dependent component of leptin-induced vasorelaxation is mediated, at least partially, by H2S.

• Authors: Anna Jamroz-Wiśniewska, Arieh Gertler, Gili Solomon, Mark E Wood, Matthew Whiteman, Jerzy Bełtowski
• Journal: PloS one (PLoS One) Vol. 9 Issue 1 Pg. e86744 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24475175 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkynes
• Biological Factors
• Leptin
• Organometallic Compounds
• Receptors, Leptin
• Salicylates
• endothelium-dependent hyperpolarization factor
• Phenylephrine
• Nitric Oxide
• bismuth subsalicylate
• propargylglycine
• Nitric Oxide Synthase Type III
• Nos3 protein, rat
• Cystathionine gamma-Lyase
• Glycine
• Bismuth
• Hydrogen Sulfide

Topics

• Adipose Tissue (blood supply, drug effects)
• Alkynes (pharmacology)
• Animals
• Biological Factors (genetics, metabolism)
• Bismuth (pharmacology)
• Cystathionine gamma-Lyase (antagonists & inhibitors, metabolism)
• Diet
• Endothelium, Vascular (drug effects)
• Gene Expression Regulation
• Glycine (analogs & derivatives, pharmacology)
• Hydrogen Sulfide (antagonists & inhibitors, metabolism)
• Leptin (metabolism, pharmacology)
• Male
• Mesenteric Arteries (drug effects)
• Nitric Oxide (antagonists & inhibitors, metabolism)
• Nitric Oxide Synthase Type III (genetics, metabolism)
• Obesity (genetics, metabolism, physiopathology)
• Organometallic Compounds (pharmacology)
• Phenylephrine (pharmacology)
• Rats
• Rats, Wistar
• Receptors, Leptin (antagonists & inhibitors, metabolism)
• Salicylates (pharmacology)
• Signal Transduction
• Tissue Culture Techniques
• Vasoconstriction (drug effects)
• Vasodilation (drug effects)