Abnormal activation of K+ channels in aortic smooth muscle of rats with endotoxic shock: electrophysiological and functional evidence

1 This study examined the role of K+ channels in Vascular hyporeactivity of rats with endotoxic shock ex vivo. 2 At the end of the in vivo experiments, thoracic aortas were removed from endotoxaemic and control rats. After removal of the endothelium, aortic seg ments were mounted in myographs for recording of isometric tension and smoo th muscle membrane potential. 3 Membrane potentials recorded from endotoxaemic rats were hyperpolarized c ompared to those of the controls. This hyperpolarization was partially reve rsed by tetraethylammonium, charybdotoxin or glibenclamide, but not signifi cantly affected by apamin. The hyperpolarization was also partially attenua ted by N-omega-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]oxadiazo lo[4,3-a]quinoxalin-1-one (ODQ). 4 In phenylephrine-contracted aortic rings, both agonists of K+ channels, N S1619 and pinacidil, induced greater relaxations and re-polarizations in th e preparations obtained from endotoxaemic rats. The NS1619-induced relaxati on and re-polarization in arteries from endotoxaemic rats were partially in hibited by tetraethylammonium and completely inhibited by charybdotoxin, L- NAME or ODQ, but not significantly affected by apamin. Similarly, the great er relaxation and re-polarization induced by pinacidil in arteries from end otoxaemic rats were also inhibited by glibenclamide, L-NAME or ODQ. However , these inhibitors had no significant effect on relaxations and repolarizat ions induced by NS1619 and pinacidil in arteries from controls. 5 This study provides the electrophysiological and functional evidence show ing an abnormal activation of K+ channels in vascular smooth muscle in anim als with endotoxic shock. Our observations suggest that overproduction of n itric oxide causes an activation of large conductance Ca2+-activated K+ cha nnels and ATP-sensitive K+ channels which contributes to endotoxin-mediated vascular hyporeactivity.