In vascular smooth muscle cells (VSMCs), the membrane depolarization caused by the activation of DAG signalling pathway leads to the opening of VOCCs channels, [Ca2+]i increase and contraction. We have previously shown an increased functional expression of a member of the TRPC family of non-selective cation channels, namely TRPC3, in mesenteric VSMC of hypertensive mice, which contributes to the increased vascular tone by favouring depolarization (Alvarez-Miguel et al. 2017). Changes in the functional expression of G-protein coupled receptors (GPCRs) could alter DAG-dependent activation of TRPC3 and hence participate in the hypertensive phenotype. Here, we explored the possible changes in the functional expression of the constituents of this signalling pathway in essential hypertension. Using a mice model of essential hypertension (BPH mice) and its normotensive controls (BPN) we explored changes on the molecular composition of the mechanotransduction signalling cascade in hypertension. We analyzed the expression and the association patron of several components of the TRPC family, GPCRs and Cl- channels by qPCR and PLA, and we explored their functional contribution to the vascular tone by electrophysiology and myography studies. BPH VSMCs showed an increased mRNA expression of P2Y2 and P2Y6 receptors, TRPC3 and Ca2+-activated Clchannels (ClCa1) and the Na+-K+-2Cl- cotransporter (NKCC1). The vasoconstrictor effects of ATP, UTP and UDP were consistent with an increased functional expression of P2Y6 receptors in BPH arteries. UTP-activated currents recorded in isolated BPN and BPH VSMCs were not different. A fraction of these currents was sensitive to niflumic acid, indicating the involvement of ClCa channels. Moreover, niflumic acid induced significant hyperpolarization in BPN and BPH mesenteric VSMC, pointing to a relevant contribution of ClCa channels to determine VSMCs resting Vm. We propose that the coordinated changes in several ionic conductances that participate in UTP-induced vasoconstriction can be relevant to explain the hypertensive phenotype.

Resumen del póster presentado al VI Meeting de la Red Española de Canales Ióniocs (RECI), celebrado en Santiago de Compostela del 6 al 8 de septiembre de 2017.

Supported by grants BFU2016-75360-R (MINECO) and by a Junta de Castilla y León and Fondo Social Europeo (FSE) fellowship to IAM.

Peer reviewed