EFFECT OF OUABAIN ON ADENOSINE RECEPTOR-MEDIATED HYPERPOLARIZATION INPORCINE CORONARY-ARTERY SMOOTH-MUSCLE

We investigated the effect of inhibitors of endothelium-derived nitric oxide and sodium-potassium (Na+-K+) pumps on adenosine receptor-media ted hyperpolarization of porcine coronary artery smooth muscle with an d without endothelium. The average resting membrane potential (RMP) in porcine coronary artery smooth muscle was -51.5 +/- 0.2 and -50.7 +/- 0.2 mV, in the presence and absence of endothelium, respectively. Nei ther ouabain, N-nitro-L-arginine methyl eater (L-NAME) nor ouabain and L-NAME in combination significantly affected the resting membrane pot ential in the absence of vasodilator agonists. Adenosine agonists, 2-c hloroadenosine and 5'-N-ethylcarboxamidoadenosine at 10(-5) M caused a significant increase in RMP with intact endothelium and caused a smal ler but significant increase in RMP in the absence of endothelium. Oua bain (10(-5) M) in the absence of L-NAME significantly reduced hyperpo larization due to 2-chloroadenosine and 5'-N-ethylcarboxamidoadenosine in the presence of endothelium. However, in the absence of endotheliu m, its inhibitory effect was not significant. When ouabain plus L-NAME (10(-5) M) were given simultaneously, the hyperpolarization caused by adenosine agonists was significantly further attenuated nearly to the RMP level. Attenuation of the response to 2-chloroadenosine and 5'-N- ethylcarboxamidoadenosine by ouabain was not reversed by the nitric ox ide precursor, L-arginine (10(-4) M) both in the presence and absence of endothelium. These results suggest that hyperpolarization of vascul ar smooth muscle of the porcine coronary artery by adenosine agonists is at least partly endothelium dependent and possibly involves the Na-K+ pump and the release of nitric oxide. (C) 1997 Elsevier Science B. V.