Effects of pyrimidines on the guinea-pig coronary vasculature

Abstract

1. The effects of the pyrimidines, uridine 5'-triphosphate (UTP), thymidine 5'-triphosphate (TTP) and cytidine 5'-triphosphate (CTP), were examined in the guinea-pig coronary bed, by use of a Langendorff technique. Comparisons were made with the actions of the purines adenosine 5'-triphosphate (ATP), inosine 5'-triphosphate (ITP) and guanosine 5'-triphosphate (GTP). The effect of, the nitric oxide synthase inhibitor, L-NG-nitroarginine methyl ester (L-NAME) and, the prostaglandin synthesis inhibitor, indomethacin on the vasodilator response to these purines and pyrimidines was examined. The effects of these inhibitors were assessed on their ability to inhibit both the amplitude and the area of the vasodilator response. 2. The relative order of potency of the purines and pyrimidines studied was ATP > UTP > ITP >> GTP, TTP, CTP. 3. The maximum amplitude and area of the vasodilator response to the pyrimidines, UTP (5 x 10(-10)-5 x 10(-7) mol), TTP (5 x 10(-8)-5 x 10(-7) mol) and CTP (5 x 10(-7) mol), and purines, ITP (5 x 10(-9)-5 x 10(-7) mol) and GTP (5 x 10(-8)-5 x 10(-7) mol), were significantly reduced by L-NAME (3 x 10(-5) and 10(-4) M). 4. The inhibition of the response to ATP (5 x 10-8 mol), UTP (5 x 10-8 mol), ITP (5 x 10-8 mol), TTP(5 x 10-7 mol), CTP (5 x 10- mol) and GTP (5 x 10- mol) by L-NAME (3 x 10-5 M) was significantly reversed by L-arginine (1.5 x 10-3 M).5. L-NAME (3 x 10-5 and 10-4 M) only inhibited the amplitude of the vasodilator response to a low dose of ATP (5 x 10-mol), although the area of vasodilator response to ATP(5 x 10-11-5 x 10-7 mol) was significantly reduced by L-NAME (3 x 10-5 and 10-4 M).6. The maximum amplitude of the vasodilator response to ATP (5 x 10-10-5 x 10-7 mol) was significantly reduced by indomethacin (10-6 M), although the area of the vasodilator response to ATP was only significantly reduced at one intermediate dose (5 x 10-9 mol). Indomethacin (10-6 M) did not affect the maximum amplitude or area of the vasodilator responses to UTP (5 x 10-11-5 x 10-7 mol),ITP (5 x 10-10-5 x 10-7 mol), CTP (5 x 10-7 mol), TTP (5 x 10-8-5 x 10-7 mol) and GTP(5 x 10-8-5 x 10-7 mol).7. It is concluded that in the guinea-pig coronary vasculature, the vasodilatation evoked by the pyrimidines, UTP, TTP and CTP, was mediated in large part via nitric oxide, as were the vasodilatations evoked by the purines ITP and GTP. The vasodilatations evoked by ATP, however, appear to involve prostanoids in addition to the release of nitric oxide.