Combined Contribution of Endothelial Relaxing Autacoides in the Rat Femoral Artery Response to CPCA: An Adenosine A2Receptor Agonist

Abstract

We examined the contribution of endothelial relaxing factors and potassium channels in actions of CPCA, potent adenosine A2receptor agonist, on isolated intact male rat femoral artery (FA). CPCA produced concentration-dependent relaxation of FA, which was notably, but not completely, reduced after endothelial denudation. DPCPX, A1receptor antagonist, had no significant effect, while SCH 58261 (A2Areceptor antagonist) notably reduced CPCA-evoked effect. Pharmacological inhibition of nitric oxide synthase or cyclooxygenase comparably reduced CPCA-evoked action, still in a lesser degree than after denudation. In the presence of buffer with high K+(100  mM), CPCA-produced relaxations were almost abolished. TEA (nonselective KCablocker), glibenclamide (KATPblocker), Ba++(KIRblocker), or ouabain (Na+/K+-ATPase inhibitor) did not change CPCA-induced relaxation. Concentration-response curve for CPCA was significantly shifted to the right after the incubation of apamin (SK channel blocker). CPCA produced concentration-dependent relaxation of FA that was partly dependent on endothelial cells. Endothelium-related portion of CPCA-elicited effect was mediated by combined action of endothelial NO, prostacyclin, and EDHF after activation of endothelial A2Areceptors. Small conductance KCachannels were involved in this action.