Differential effects of ATP- and 2-methylthioATP-induced relaxation in guinea pig coronary vasculature
Vials, A.J.; Burnstock, G.
Journal of Cardiovascular Pharmacology 23(5): 757-764
1994
ISSN/ISBN: 0160-2446 PMID: 7521458 Document Number: 429840
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) gt ATP gt beta,gamma-methyleneATP (beta,gamma-meATP) gtoreq alpha,beta-methyleneATP (alpha,beta-meATP), thus establishing the presence of P-2ypurinoceptors in this preparation. L-N-nitroarginine methyl ester (L-NAME, 3 times 10-5M 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 times 10-12-5 times 10-9' mol). However, for ATP (5 times 10-7-5 times 10-10 mol), L-NAME 3 times 10-5M 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 times 10 -10 MOI). L-Arginine 1.5 times 10-3M significantly reversed inhibition of the area under the flow-time curve of the response to 2-meSATP 5 times 10-10 mol and ATP 5 times 10-8 mol by L-NAME 3 times 10-5M. The maximum decrease in perfusion pressure of the response to ATP 5 times 10-10-5 times 10-7 mol was significantly attenuated in the presence of indomethacin 10-6M. In contrast, indomethacin 10-6M did not reduce the response to 2-meSATP and adenosine except at low doses (5 times 10-11 and 5 times 10-11-5 times 10-10 mol, respectively). 8-(p-Sulfophenyl)theophylline (8-PSPT, 3 times 10-5M, a nonselective P-1-purinoceptor antagonist, did not affect the response to ATP except at low doses (5 times 10-10 mol). 8-PSPT 3 times 10-5M significantly reduced the vasodilatation produced in response to adenosine 5 times 10-10-5 times 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-2ypurinoceptors to induce relaxation through production or release of nitric oxide (NO). ATP is less potent than 2meSATP at this receptor, but has an additional vasodilator action through prostanoids.