The role of protease-activated receptors on the intracellular calcium ion dynamics of vascular smooth muscles, with special reference to cerebral arterioles

Abstract

Protease-activated receptors (PARs) mediate cellular responses to various proteases in numerous cell types, including smooth muscles and the endothelium of blood vessels. To clarify whether the stimulation of PARs induces responses in smooth muscle cells of cerebral arterioles, intracellular Ca2+([Ca2+]i) dynamics and nitric oxide (NO) production during PARs stimulation were investigated in the rat cerebral arterioles by real-time confocal microscopy, since [Ca2+]i and NO are both key factors in the maintenance of strain in blood vessels. Testicular arterioles were also investigated for comparison. In smooth muscle cells of small cerebral arterioles (< 50 microm in diameter), thrombin and PAR1-activating peptide (AP) induced an increase in [Ca2+]i and contraction. The response to PAR1 activation was caused by Ca2+ mobilization from intracellular Ca2+ stores. Trypsin and PAR2-AP induced a decrease in [Ca2+]i in the cells which was considered to be mediated by endothelium-derived NO and/or by promoting a Ca2+ sequestration mechanism. PAR3- and 4-AP had little effect. In contrast to small cerebral arterioles, [Ca2+]i dynamics in smooth muscle cells of large cerebral arterioles (< 150 microm in diameter) or testicular arterioles remained unchanged during PARs activation. The effects of PARs activation on the [Ca2+]i dynamics and the contraction/relaxation of cerebral arterioles are also discussed in relation to the role of proteases in the regional tissue circulation of the brain.