Beta-adrenoceptor-mediated relaxation inhibited by tetrapentylammonium ions in rat mesenteric artery

The aim of this study was to examine the contribution of K+ channel activation to beta-adrenoceptor-mediated relaxation in rat mesenteric arteries. Isoprenaline and fenoterol concentration-dependently relaxed the phenylephrine-preconstricted endothelium-intact arteries of the rat with EC50 values of 0.26 +/- 0.03 microM and 0.87 +/- 0.12 microM, respectively. Beta-adrenoceptor-mediated relaxation was significantly attenuated upon removal of endothelium. Tetrapentylammonium ions (TPA+) at low concentrations (1-5 microM) inhibited relaxations induced by beta-adrenoceptor agonists in arteries with and without endothelium, while glibenclamide (3 microM) had no effect. TPA+ (5 microM) inhibited isoprenaline-induced relaxation in the presence of either iberiotoxin (100 nM) or glibenclamide (3 microM). TPA+ did not alter forskolin-induced relaxation. In the presence of 60 mM extracellular K+, the relaxations induced by two agonists were reduced in endothelium-intact arteries and abolished in endothelium-denuded arteries. The present results suggest that the activation of TPA+-sensitive K+ channels contributes toward the relaxations mediated through beta- and beta2-adrenoceptor stimulation in rat mesenteric arteries.