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Vascular smooth muscle-specific deletion of the leptin receptor attenuates leptin-induced alterations in vascular relaxation.

ABSTRACT: Obesity is a risk factor for cardiovascular disease and is associated with increased plasma levels of the adipose-derived hormone leptin. Vascular smooth muscle cells (VSMC) express leptin receptors (LepR); however, their physiological role is unclear. We hypothesized that leptin, at levels to mimic morbid obesity, impairs vascular relaxation. To test this, we used control and VSM-LepR knockout mice (VSM-LepR KO) created with a tamoxifen-inducible specific Cre recombinase to delete the LepR gene in VSMC. Control (10-12 wk old) and VSM-LepR KO (10-12 wk old) mice were fed a diet containing tamoxifen (50 mg/kg) for 6 wk, after which vascular reactivity was studied in isolated carotid arteries using an organ chamber bath. Vessels were incubated with leptin (100 ng/ml) or vehicle (0.1 mM Tris·HCl) for 30 min. Leptin treatment resulted in significant impairment of vessel relaxation to the endothelial-specific agonist acetylcholine (ACh). When these experiments were repeated in the presence of the superoxide scavenger tempol, relaxation responses to ACh were restored. VSM-LepR deletion resulted in a significant attenuation of leptin-mediated impaired ACh-induced relaxation. These data show that leptin directly impairs vascular relaxation via a VSM-LepR-mediated mechanism, suggesting a potential pathogenic role for leptin to increase cardiovascular risk during obesity.

SUBMITTER: Ryan MJ

PROVIDER: S-EPMC4896083 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Vascular smooth muscle-specific deletion of the leptin receptor attenuates leptin-induced alterations in vascular relaxation.

Ryan Michael J MJ Coleman T Taylor TT Sasser Jennifer M JM Pittman Katarina M KM Hankins Michael W MW Stec David E DE

American journal of physiology. Regulatory, integrative and comparative physiology 20160302 10

Obesity is a risk factor for cardiovascular disease and is associated with increased plasma levels of the adipose-derived hormone leptin. Vascular smooth muscle cells (VSMC) express leptin receptors (LepR); however, their physiological role is unclear. We hypothesized that leptin, at levels to mimic morbid obesity, impairs vascular relaxation. To test this, we used control and VSM-LepR knockout mice (VSM-LepR KO) created with a tamoxifen-inducible specific Cre recombinase to delete the LepR gene ...[more]

PMID: 26936780

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Vascular smooth muscle-specific deletion of the leptin receptor attenuates leptin-induced alterations in vascular relaxation.

Publications

Vascular smooth muscle-specific deletion of the leptin receptor attenuates leptin-induced alterations in vascular relaxation.

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