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This Article Full Text Full Text (PDF) All Versions of this Article: 294/3/E481    most recent 00103.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Juan, C.-C. Articles by Ho, L.-T. Search for Related Content PubMed PubMed Citation Articles by Juan, C.-C. Articles by Ho, L.-T.

Leptin increases endothelin type A receptor levels in vascular smooth muscle cells

¹Institute of Physiology, ²Department of Surgery, and ³Faculty of Medicine, School of Medicine, National Yang-Ming University; ⁴Division of Endocrinology and Metabolism, Department of Medicine, and ⁵Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan

Submitted 15 February 2007 ; accepted in final form 22 November 2007

Leptin, one of the adipocyte-secreted peptides, is involved in the control of appetite and body weight. Several studies have demonstrated that plasma leptin levels are elevated in obese subjects and are positively correlated with body weight. The arterial endothelin (ET) system plays an important role in the regulation of vascular tone, and ET-1 overexpression may be involved in the pathogenesis of the hypertension associated with insulin resistance. This study was performed to explore the regulatory effects of leptin on ET receptor expression and ET binding in A10 vascular smooth muscle cells (VSMCs) by use of Northern blotting, immunoblotting, and a ¹²⁵I-labeled ET-1 binding assay. The effect of leptin on ET receptor-mediated cell proliferation was also tested. The results showed that leptin caused a significant increase in [¹²⁵I]-ET-1 binding, which was time- and dose-dependent. Immunoblotting showed that expression of the ET type A receptor (ET_AR) in leptin (10^–7 M)-treated cells was increased by up to 2.3-fold compared with controls. Levels of ET_AR mRNA measured by Northern blotting were also increased by up to 2.2-fold in leptin (10^–7 M)-treated cells. Pretreatment with an ERK inhibitor, PD-98059 (2.5 x 10^–5 M), blocked the leptin-induced increase in ¹²⁵I-ET-1 binding. Finally, ET-1 (10^–7 M)-stimulated cell proliferation was enhanced by leptin (10^–7 M) pretreatment, with a maximal increase of twofold compared with controls. In conclusion, leptin increases ET_AR expression in VSMCs in a time- and dose-dependent manner. This effect is ERK dependent and is associated with increased ET-1-stimulated cell proliferation. These findings provide support for roles for leptin and the ET system in the pathogenesis of obesity-associated hypertension.

endothelin-1; proliferation; leptin receptor; extracellular signal-regulated kinase