In vascular smooth muscle cells (VSMCs), voltage operated Ca2+ channels (VOCC) transduce cell surface membrane potential (EM) changes into local intracellular calcium transients that initiate contraction events. VOCCs activate in response to membrane depolarization with a steep voltage-dependence, so that small changes in EM dramatically affect their open probability. Membrane depolarization can be triggered by agonist-induced activation of the DAG signalling pathways, which in turn activate non-selective cation channels that depolarize and constrict VSMCs. Some of the members of the TRPC family, such as TRPC3 channels, have been identified as the responsible for the agonist-induced depolarization of VSMCs..Essential hypertension involves a gradual, sustained increase in total peripheral resistance caused by an increased vascular tone. The mechanisms underlying this change in vascular function are the subject of intense investigation, and a model has been proposed in which the combination of membrane depolarization and higher VOCCs activity conspires to generate high Ca2+ influx, contraction, and vasoconstriction. Due to their role in agonist-induced depolarization, changes in the expression and/or the activity of TRPC3 channels in VSMCs could contribute to the more depolarized EM observed in hypertensive models. We have used a genetic mouse model of essential hypertension (BPH mice) and its normotensive controls (BPN) to study the functional expression of TRPC3 channels in mesenteric arteries VSMCs and their contribution to vascular tone.Animal protocols were approved by the Institutional Care and Use Committee of our Institution. Mice were killed by decapitation after isofluorane anaesthesia (5% at 2.5 l min-1 O2), and mesenteric VSMCs were obtained by enzymatic dissociation. Expression and function of TRPC3 in VSMCs form BPN and BPH VSMCs was explored with real-time PCR, electrophysiological recordings in isolated VSMCs and pressure myography in intact vessels.qPCR showed an increased expression of TRPC3 mRNA in BPH mesenteric VSMCs. Electrophysiological studies in isolated VSMCs show the presence of non-selective cationic currents activated by bath application of several agonists, including phenylephrine, ATP and UTP, as well as by direct application of OAG, that could be blocked by the TRPC3 antagonists Pyr3 and Pyr10 in a dose-dependent manner. In pressurized mesenteric vessels application of phenylephrine induced a vasoconstriction that was fully reversed by Pyr3 application. We excluded a non-specific effect of Pyr3 on VOCC that could contribute to the observed vasodilation. Our data suggest that TRPC3 channels could represent good candidates to contribute to the natural history of hypertension.