期刊
CIRCULATION
卷 120, 期 9, 页码 753-U84出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCULATIONAHA.109.853077
关键词
hypertension; obesity; receptors, adrenergic, alpha; nervous system, sympathetic; vasoconstriction; arteries; blood pressure
资金
- National Institutes of Health [R01 HL067533]
- American Heart Association postdoctoral fellowship
Background-Obesity causes hypertension and sympathoactivation, a process proposed to be mediated by leptin. Protein tyrosine phosphatase 1B (PTP1B), a major new pharmaceutical target in the treatment of obesity and type II diabetes mellitus, constrains the metabolic actions of leptin, but the extent to which PTP1B regulates its cardiovascular effects is unclear. This study examined the hypothesis that PTP1B is a negative regulator of the cardiovascular effects of leptin. Methods and Results-PTP1B knockout mice had lower body fat but higher mean arterial pressure (116 +/- 5 versus 105 +/- 5 mm Hg, P < 0.05) than controls. Leptin infusion produced a greater anorexic effect in PTP1B knockout mice and a marked increase in mean arterial pressure (135 +/- 5 mm Hg) in PTP1B knockout mice only. The decrease in mean arterial pressure in response to ganglionic blockade was higher in PTP1B knockout mice (-38 +/- 3% versus -29 +/- 3%, P < 0.05), which suggests increased sympathetic tone. PTP1B deletion blunted mean arterial pressure responses to phenylephrine injection (55 +/- 10% versus 93 +/- 7%, P < 0.05). Phenylephrine-induced aortic contraction was reduced in PTP1B knockout mice (57.7 +/- 9% versus 96.3 +/- 12% of KCl, P < 0.05), consistent with desensitization to chronically elevated sympathetic tone. Furthermore, PTP1B deletion significantly reduced gene expression of 3 alpha(1)-adrenergic receptor subtypes, consistent with blunted constriction to phenylephrine. Conclusions-These data indicate that PTP1B is a key regulator of the cardiovascular effects of leptin and that reduced vascular adrenergic reactivity provides a compensatory limit to the effects of leptin on mean arterial pressure. (Circulation. 2009;120:753-763.)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据