Leptin-Induced Endothelium-Dependent Vasorelaxation of Peripheral Arteries in Lean and Obese Rats: Role of Nitric Oxide and Hydrogen Sulfide |
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| Authors: | Anna Jamroz-Wi?niewska Arieh Gertler Gili Solomon Mark E. Wood Matthew Whiteman Jerzy Be?towski |
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| Affiliation: | 1. Department of Pathophysiology, Medical University, Lublin, Poland.; 2. Department of Neurology, Medical University, Lublin, Poland.; 3. Institute of Biochemistry, Food Science and Nutrition, The Hebrew University of Jerusalem, Rehovot, Israel.; 4. Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom.; 5. University of Exeter Medical School, St Luke’s Campus, Exeter, Devon, United Kingdom.; Medical School of Hannover, Germany, |
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| 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. |
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