P2 purinoceptor-mediated dilations in the rat middle cerebral artery after ischemia-reperfusion.
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| Abstract |
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.
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| Authors | S P Marrelli, A Khorovets, T D Johnson, W F Childres, R M Bryan Jr |
| Journal | The American journal of physiology (Am J Physiol) Vol. 276 Issue 1 Pg. H33-41 (01 1999) ISSN: 0002-9513 [Print] United States |
| PMID | 9887014 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.) |
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