ATP‐induced local and conducted vasomotor mechanisms in isolated rat cerebral penetrating arterioles

Abstract

Background ATP is a regulator in the cerebral circulation and initiates conducted vasomotor responses. We analyzed the mechanism of ATP-induced local and conducted vasomotor responses in rat cerebral penetrating arterioles. Methods Arterioles were cannulated and their internal diameter monitored with a video microscope. Vasomotor responses to micro-application of ATP were obtained in the presence or absence of inhibitors. Intracellular membrane potentials of smooth muscle cells were measured in some vessels. Results Topical micro-application of ATP produced a biphasic response (constriction followed by dilation), resulting in conducted vasomotor responses. Conducted dilation was preceded by membrane hyperpolarization. a.b-methylene-ATP or pyridoxal phosphate-6-azophenyl-2′,4′-disulphonic acid blunted the ATP-mediated constriction and enhanced the dilation. No-monomethyl-L-arginine, clotrimazole, and endothelial impairment inhibited the local dilation of ATP. In contrast, the conducted dilation was attenuated by clotrimazole, MS-PPOH and endothelial impairment, but not No-monomethyl-L-arginine. Conclusions Our results indicate that 1) ATP-induced conducted dilation is preceded by hyperpolarization; 2) ATP induces initial local constriction via smooth muscle P2X1 and secondary dilation via endothelial P2Y2 receptors in the cerebral arterioles; 3) Nitric oxide and cytochrome P-450 metabolites contribute to local dilation of ATP; 4) ATP-induced conducted dilation is regulated by the endothelium and cytochrome P-450 metabolites. NIH HL57540 (HHD) and NS30555 (RGD and HHD).