Genetic deletion of the TRPC3 channel blunts the development of angiotensin II‐induced hypertension in mice

Abstract

The Transient Receptor Potential Channel 3 (TRPC3) is a cation – conducting channel in the plasma membrane of vascular smooth muscle cells, which is activated by G‐protein coupled receptors (GPCR) including the α1‐adrenergic receptor. Several reports indicate that TRPC3 are upregulated in arteries of hypertensive animals and humans, but the lack of a selective TRPC3 blocker has thwarted efforts to define its role in blood pressure elevation. Here, we used TRPC3−/− mice to define the contribution of TRPC3 to the pathogenesis of hypertension. TRPC3 mRNA level was similar between mesenteric arteries (MA) of Ang II‐ and saline‐infused WT mice, but TRPC3 protein expression was ~5.7‐fold higher in MA of hypertensive mice. Resting mean arterial pressure (MAP) was not different between TRPC3−/− and WT mice (119±3 vs. 125±3 mm Hg; n=8–10). However, Ang II infusion for 14 days increased MAP in WT mice to 170±3 mm Hg compared to only 146±4 mm Hg in TRPC3−/− mice. PE‐induced constrictions were blunted in pressurized MA of Ang II‐infused TRPC3−/− (53±2%) compared to WT mice (71±5%), and PE‐evoked cation current was lower in patch‐clamped VSMCs of Ang II‐infused TRPC3−/− mice (‐2.5±0.5 pA/pF) compared to WT animals (−5.4±0.6 pA/pF). Thus, TRPC3 appears to importantly contribute to Ang II‐induced hypertension possibly by mediating GPCR cation current in VSMCs. NIH R01 HL064806 (NJR), AHA 12PRE11850002 (ARP) and NIH Z01‐ES‐101684 (LB)