Transient receptor potential canonical type 3 channels and blood pressure in humans

Objective There is evidence that transient receptor potential canonical type 3 (TRPC3) cation channels are involved in the regulation of blood pressure, but this has not been studied using human renal tissue. We tested the hypothesis that the expression of TRPC3 in human renal tissue is associated with blood pressure in patients. Material and methods TRPC3 was detected in cultured human endothelial cells and in vascular endothelium cells from human renal tissue by immunoblotting, immunohistochemistry, and quantitative real-time reverse transcriptase-PCR. The changes of TRPC3 and vascular endothelial growth factor receptor type 2 expression in cultured human endothelial cells were measured after administration of vascular endothelial growth factor isoform 121. Results In cultured human endothelial cells, vascular endothelial growth factor isoform 121 significantly reduced TRPC3 expression by 57% and vascular endothelial growth factor receptor type 2 by 70%. This reduction was partly blocked by phosphatidylinositol 3-kinase inhibitors, wortmannin, or LY294002. Downregulation of TRPC3 channel expression was associated with reduced calcium influx. The changes of calcium influx could be abolished by the inhibitor of TRPC channels, 2-aminoethoxydiphenylborane, pointing to their functional importance. TRPC3 expression was significantly higher in patients with SBP more than 140mmHg compared with patients with SBP of 140mmHg or less (0.00181 +/- 0.00059 versus 0.00037 +/- 0.00012 arbitrary units; P < 0.01). Conclusion The data support the hypothesis that TRPC3 expression in human renal tissue including vascular endothelium is associated with blood pressure regulation in humans. J Hypertens 27:1217-1223 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.