Vasodilatation produced by adenosine in isolated rat perfused mesenteric artery: a role for endothelium

Abstract

Adenosine and adenosine triphosphate (ATP) induced vasodilatation was studied in isolated rat perfused mesenteric artery at constant flow. Decrease in perfusion pressure was measured after induction of tone by continuous infusion with phenylephrine (5–7 μM). Adenosine and ATP caused dose-dependent vasodilatation. Following infusion with selective A₂ adenosine receptor antagonist, 3,7-dimethyl-l-propargylxanthine (DMPX) (10 μM), or non-selective adenosine receptor antagonist, theophylline (30 μM), vasodilatation produced by adenosine were significantly reduced at lower doses. Responses to adenosine were not affected by pretreatment of tissues with either the P₂-purinoceptor desensitizing agent, α, β methylene ATP (30 μM), or the P₂-purinoceptor antagonist, suramin (10 μM). In contrast, both α, β methylene ATP and suramin significantly attenuate relaxation produced by ATP. Further, it was found that relaxation elicited by either adenosine or ATP was not significantly affected by the presence of glibenclamide (30 μM). Vasodilatation induced by adenosine and ATP was greatly reduced in denuded arteries but more so for ATP than adenosine. It is concluded that adenosine-mediated vasodilatation may hardly be due to the stimulation of A₂ adenosine receptors and is strongly dependent on the presence of functional endothelium whereas ATP-mediated vasodilator responses were mediated via the activation of P_2y-purinoceptors and appeared to be entirely dependent upon the presence of functional endothelium. Further, vasodilator responses to neither adenosine nor ATP were sensitive to inhibition by the potassium channel blocker glibenclamide, in isolated mesenteric perfused bed. This would imply that ATP-sensitive potassium channels were not involved in adenosine and ATP mediated vasodilatation.