P2 purinoceptor-mediated dilations in the rat middle cerebral artery after ischemia-reperfusion.
Endothelial-mediated dilations to selective P2Y1 and P2Y2 purinoceptor agonists [2-methylthioadenosine triphosphate (2MeS-ATP) and uridine 5'-triphosphate (UTP), respectively] were evaluated in middle cerebral arteries (MCAs) of rats after 2 h of ischemia followed by 24 h of reperfusion (I/R). MCAs were harvested, pressurized to 85 mmHg, and luminally perfused. 2MeS-ATP, which dilates by the synthesis and release of nitric oxide (NO), had significantly reduced maximum dilations following I/R. Reduced smooth muscle sensitivity to NO may explain the reduced dilation to 2MeS-ATP. In contrast, the dilations elicited by UTP were potentiated in that the concentration of agonist necessary to produce one-half of the maximum dilation was reduced by 75%. The potentiated dilation to UTP was the result of an endothelial factor having all the characteristics of the endothelium-derived hyperpolarizing factor (EDHF). That is, it was neither NO nor a cyclooxygenase metabolite, and its actions involved calcium-activated potassium channels and smooth muscle hyperpolarization. We conclude that the effect of I/R on endothelial-mediated dilations depends on the receptor system and the mechanism of dilation. Dilations elicited by 2MeS-ATP were attenuated, while dilations UTP were potentiated due to the upregulation of the EDHF mechanism.
Marrelli
S P
SP
The Graduate Program in Cardiovascular Sciences of the DeBakey Heart Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Khorovets
A
A
Johnson
T D
TD
Childres
W F
WF
Bryan
R M
RM
D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D002536:Cerebral Arteries / Q000503:physiopathology*; D006224:Cricetinae; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; D015427:Reperfusion Injury / Q000503:physiopathology*; D014664:Vasodilation / Q000502:physiology*; D014666:Vasomotor System / Q000503:physiopathology
C546384:P2ry1 protein, rat; C546387:P2ry2 protein, rat; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; D009569:Nitric Oxide