Potential effect of resistin on the ET‐1‐increased reactions of blood pressure in rats and Ca 2+ signaling in vascular smooth muscle cells

Resistin and endothelin‐1 (ET‐1) are upregulated in people with type II diabetes mellitus, central obesity, and hypertension. ET‐1 signaling is involved in Ca 2+ ‐contraction coupling and related to blood pressure regulation. The aim of this study is to investigate the role of resistin on ET‐1‐increased blood pressure and Ca 2+ signaling. The blood pressure and cytosolic Ca 2+ of vascular smooth muscle cells (VSMCs) of Sprague–Dawley rats were detected. The data demonstrated that resistin accelerated and prolonged ET‐1‐induced increases in blood pressure and had significant effects on ET‐1‐increased Ca 2+ reactions. Resistin‐enhanced ET‐1‐increased Ca 2+ reactions were reversed by blockers of store‐operated Ca 2+ entry (SOCE) and extracellular‐signal‐regulated kinase (ERK). The endogenous expression of Orai and stromal interaction molecular (STIM) were characterized in the VSMCs. Furthermore, resistin‐enhanced ET‐1 Ca 2+ reactions and the resistin‐dependent activation of SOCE were abolished under STIM1‐siRNA treatment, indicating that STIM1 plays an important role in resistin‐enhanced ET‐1 Ca 2+ reactions in VSMCs. Resistin appears to exert effects on ET‐1‐induced Ca 2+ increases by enhancing the activity of ERK‐dependent SOCE (STIM1‐partcipated), and may accelerate and prolong ET‐1‐increased blood pressure via the same pathway. J. Cell. Physiol. 227: 1610–1618, 2012. © 2011 Wiley Periodicals, Inc.