P 2u Receptor–Mediated Release of Endothelium-Derived Relaxing Factor/Nitric Oxide and Endothelium-Derived Hyperpolarizing Factor From Cerebrovascular Endothelium in Rats

Publisher Website
Google Scholar
Abstract
Background and Purpose —Stimulation of P 2u purinoceptors by UTP on endothelium dilates the rat middle cerebral artery (MCA) through the release of endothelium-derived relaxing factor/nitric oxide (EDRF/NO) and an unknown relaxing factor. The purpose of this study was to determine whether this unknown relaxing factor is endothelium-derived hyperpolarizing factor (EDHF). Methods —Rat MCAs were isolated, cannulated, pressurized, and luminally perfused. UTP was added to the luminal perfusate to elicit dilations. Results —Resting outside diameter of the MCAs in one study was 209±7 μm (n=10). The MCAs showed concentration-dependent dilations with UTP administration. Inhibition of NO synthase with N G -nitro- l -arginine methyl ester (L-NAME) (1 μmol/L to 1 mmol/L) did not diminish the maximum response to UTP but did shift the concentration-response curve to the right. Scavenging NO with hemoglobin (1 or 10 μmol/L) or inhibition of guanylate cyclase with ODQ (1 or 10 μmol/L) had effects on the UTP-mediated dilations similar to those of L-NAME. In the presence of L-NAME, dilations induced by 10 μmol/L UTP were accompanied by 13±2 mV ( P Conclusions —Stimulation of P 2u purinoceptors on the endothelium of the rat MCA released EDHF, in addition to EDRF/NO, and dilated the rat MCA by opening an atypical calcium-activated K channel.