Contribution of ATP-sensitive potassium channels to beta-adrenoceptor-mediated responses

In isolated hearts the inotropic response to the beta-adrenoceptor agonist isoproterenol is known to be abolished after ischaemia and reperfusion. The aim of this study was to investigate whether at decreased glucose levels the beta-adrenoceptor-mediated responses in vascular smooth muscle would be depressed, since low glucose conditions mimic the influence of ischaemia. Accordingly, we investigated the influence of low glucose levels in the extracellular space on the vasorelaxation induced by isoproterenol and salbutamol in rat isolated thoracic aortic ring preparations with an intact endothelium and we attempted to further analyze the underlying mechanisms. Therefore, forskolin, dibutyryl-cAMP and glibenclamide (an ATP-sensitive K(+)-channel blocker) were studied as well. In a glucose-free medium the concentration-response curve for isoproterenol was shifted to the left compared to that obtained under normal glucose conditions. The maximal relaxation induced by isoproterenol was not affected by the absence of glucose. In contrast, the maximal relaxation induced by salbutamol in glucose-free medium decreased by 50% compared to that obtained under normal glucose conditions. Glibenclamide caused a concentration-dependent decrease of the maximum relaxation by isoproterenol in a glucose-free medium, but had no effect under normal glucose conditions. Glibenclamide did not influence the concentration-response curves for salbutamol, neither in the presence nor in the absence of glucose in the medium. The relaxation caused by forskolin and dibutyryl-cAMP was not influenced by glibenclamide in a medium devoid of glucose. In endothelium-denuded preparations glibenclamide did not affect isoproterenol-induced responses neither in the presence nor in the absence of glucose. It is concluded that beta-adrenoceptor stimulation opens ATP-sensitive potassium channels under conditions of impaired ATP-metabolism by a cAMP-independent pathway, which needs an intact endothelium.