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.
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