Contribution of P1-(A2b subtype) and P2-purinoceptors to the control of vascular tone in the rat isolated mesenteric arterial bed

Abstract

1. The direct vascular effects of adenosine and ATP were compared in the isolated and perfused mesenteric arterial bed of the rat. The actions of analogues of adenosine and ATP were also examined. 2. In preparations at basal tone, adenosine lacked vasoconstrictor actions, while ATP elicited dose-dependent vasoconstrictor responses. When the tone of preparations was raised by adding methoxamine to the perfusate, adenosine and its stable analogue, 2-chloroadenosine (2-CADO) elicited dose-dependent vasodilation. The A2 adenosine receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA) was active at lower doses than adenosine, while the A2a-selective agonist, CGS 21680 and the selective A1 agonist, N6-cyclopentyladenosine (CPA) failed to induce vasodilatation. ATP and its analogue, 2-methylthio ATP, elicited dose-dependent vasodilatation at doses 400 fold lower than adenosine. 3. Vasodilator responses to adenosine and 2-CADO were sensitive to antagonism by 1 microM 8-sulphophenyltheophylline (8-SPT) and were unaffected by inhibition of nitric oxide synthase by N omega-nitro-L-arginine methyl ester (L-NAME). In contrast, vasodilator responses to ATP were not sensitive to antagonism by 8-SPT and were almost abolished by L-NAME treatment. 4. These results indicate that in the rat mesenteric arterial bed, while both adenosine and ATP participate in the purinergic control of vascular tone, adenosine appears to be a weaker vasodilator than ATP and lacks vasoconstrictor action. A2b adenosine receptors account for the adenosine-induced vasodilatation which is independent of the production of nitric oxide.