Enhanced beta-receptor-mediated vasorelaxation in hypoxic porcine coronaryartery

To investigate the beta-adrenoceptor-mediated responses in hypoxic coronary arteries, we studied the effect of isoproterenol (Iso) on isolated porcine coronary arteries contracted with endothelin-1 in media aerated with 0, 5, 7.5, and 95% O-2. The concentration-response curve of Iso was significantl y shifted to the left by hypo;da (0 and 5% O-2). In oxygenated and hypoxic arteries, 3 x 10(-8), 10(-6), and 10(-5) M Iso significantly increased the contents of cAMP. However, there was no difference in the increases of cAMP content induced by 3 x 10(-8) M Iso between oxygenated and hypoxic arterie s. The content of cAMP induced by high concentrations of Iso (10(-6) and 10 (-5) M) was significantly larger in hypoxic than in oxygenated arteries. Fu rthermore, the potentiation by hypoxia of the Iso-induced vasorelaxation wa s inhibited by glibenclamide and depolarization by KCl, but not by removal of endothelium and indomethacin. The vasodilatory response to forskolin and dibutyryl cAMP was unaffected by hypoxia. We conclude that activation of t he ATP-sensitive K+ channel may account for the potentiation of the respons e to Iso in hypoxic coronary arteries.