whether TRPC3 up-regulation in aorta from SHR is associated with angiotensin II receptor (AT1R) mediate calcium influx. Methods: Blood pressure was measured using tail-cuff plethys-mography and a pressure transducer. Vasoconstriction of aortic rings was measured by organ chamber. Aortic smooth muscle cells (VSMCs) was cultured. Cytosolic calcium concentration was measured by the fluorescence technique. TRPC3 and AT1R expressions were detected by western blotting. Results TRPC3 expression was significantly increased in aorta form SHR compared to WKY (1.48 0.05 vs. 1.00 0.06, p 0.01). AT1R expression was no significantly difference in aorta from SHR compared to WKY (p 0.05). Administration of Ang II significantly increased TRPC3 expression in VSMCs from SHR compared to SHR control conditions (p 0.05). Administration of telmisartan, an AT1R blocker, significantly down regulated TRPC3 expression in cultured VSMCs (p 0.05). Immuno-fluorescence showed that TRPC3 and AT1R coexisted in cultured VSMC. Ang II significantly increased mean arterial blood pressure in SHR compared to WKY (53 3 vs. 22 4 mmHg, p 0.01). AngII-induced vasoconstriction was significantly higher in aortic rings from SHR compared to WKY (82 3% vs. 54 6%, p 0.01). After administration of telmisartan (5mg/kg/day) in SHR for 4 weeks systolic blood pressure was significantly reduced from 202 20 mmHg to 124 18 mmHg (n 6, p 0.01). Upregulation of TRPC3 by overexpressing TRPC3 gene in the cultured VSMCs significantly increased TRPC3 expression (p 0.01), and AngII-induced calcium influx was significantly increased to 155 12% (n 6; p 0.01). After siRNA against TRPC3 significantly reduced TRPC3 expression by 30 5% in the cultured VSMCs and Ang II-induced calcium influx was accompanied reduced (p 0.05). Conclusion This study for the first time highlights the importance of AT1R mediated the calcium influx through TRPC3 channel in genetic hypertension (supported by 973 program 2006CB503804).