DIFFERENTIAL-EFFECTS OF ATP-INDUCED AND 2-METHYLTHIOATP-INDUCED RELAXATION IN GUINEA-PIG CORONARY VASCULATURE

The Langendorff heart preparation was used to investigate the mechanism of action of vasodilatation evoked by ATP and its analogues in guinea pig coronary vasculature. The relative order of potency of ATP and its analogues in causing a reduction in perfusion pressure was 2-methylthioATP (2-meSATP) > ATP > beta,gamma-methyleneATP (beta,gamma-meATP) greater than or equal to alpha,beta-methyleneATP (alpha,beta-meATP), thus establishing the presence of P-2y-purinoceptors in this preparation. L-N-G-nitroarginine methyl ester (L-NAME, 3 x 10(-5) M) significantly attenuated both the area under the flow-time curve and the maximum decrease in perfusion pressure of the vasodilatation produced in response to 2-meSATP (5 x 10(-12)-5 x 10(-9) mol). However, for ATP (5 x 10(-7)-5 x 10(-10) mol), L-NAME 3 x 10(-5)M significantly attenuated the area under the flow-time curve of the response but did not reduce the maximum decrease in perfusion pressure except at one low dose (5 x 10(-10) mol). L-Arginine 1.5 x 10(-3)M significantly reversed inhibition of the area under the flow-time curve of the response to 2-meSATP 5 x 10(-10) mol and ATP 5 x 10(-8) mol by L-NAME 3 x 10(-5)M. The maximum decrease in perfusion pressure of the response to ATP 5 x 10(-10)-5 x 10(-7) mol was significantly attenuated in the presence of indomethacin 10(-6)M. In contrast, indomethacin 10(-6)M did not reduce the response to 2-meSATP and adenosine except at low doses (5 x 10(-11) and 5 x 10(-11)-5 x 10(-10) mol, respectively). 8-(p-Sulfophenyl)theophylline (8-PSPT, 3 x 10(-5)M), a nonselective P-1-purinoceptor antagonist, did not affect the response to ATP except at low doses (5 x 10(-10) mol). 8-PSPT 3 x 10(-5)M significantly reduced the vasodilatation produced in response to adenosine 5 x 10(-10)-5 x 10(-8) mol without having any effect on the response to 2-meSATP. It is concluded that in the guinea pig coronary vasculature, 2-meSATP acts at P-2y-purinoceptors to induce relaxation through production or release of nitric oxide (NO). ATP is less potent than 2-meSATP at this receptor, but has an additional vasodilator action through prostanoids.