TY - JOUR PY - 2002// TI - Role of cytoplasmic phospholipase A2 in endothelium-derived hyperpolarizing factor dilations of rat middle cerebral arteries JO - Journal of cerebral blood flow and metabolism A1 - You, Junping A1 - Marrelli, Sean P. A1 - Bryan, Robert M. SP - 1239 EP - 1247 VL - 22 IS - 10 N2 - Very little is known regarding the mechanism of action for the endothelium-derived hyperpolarizing factor (EDHF) response in cerebral vessels. The authors tested two hypotheses: (1) activation of the cytoplasmic form of phospholipase A (cPLA ) is involved with EDHF-mediated dilations in rat middle cerebral arteries; and (2) activation of the cPLA involves an increase in endothelial Ca through activation of phospholipase C. Middle cerebral arteries were isolated from the rat, pressurized to 85 mm Hg, and luminally perfused. The EDHF response was elicited by luminal application of uridine triphosphate (UTP) after NO synthase and cyclooxygenase inhibition (10 mol/L -nitro-l-arginine methyl ester and 10 mol/L indomethacin, respectively). AACOCF and PACOCF, inhibitors of cPLA (Ca -sensitive) and Ca -insensitive PLA (iPLA ), dose dependently attenuated the EDHF response. A selective inhibitor for iPLA2, haloenol lactone suicide substrate, had no effect on the EDHF response. The EDHF response elicited by UTP was accompanied by an increase in endothelial Ca (144 to 468 nmol/L), and the EDHF dilation was attenuated with U73122, a phospholipase C inhibitor. The authors conclude that the EDHF response elicited by luminal UTP in rat middle cerebral arteries involved activation of phospholipase C, an increase in endothelial Ca, and activation of cPLA.
Language: en
LA - en SN - 0271-678X UR - http://dx.doi.org/10.1097/01.WCB.0000037996.34930.2E ID - ref1 ER -