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

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Abstract
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 segments were mounted in myographs for recording of isometric tension and smooth muscle membrane potential. 3. Membrane potentials recorded from endotoxaemic rats were hyperpolarized compared to those of the controls. This hyperpolarization was partially reversed by tetraethylammonium, charybdotoxin or glibenclamide, but not significantly affected by apamin. The hyperpolarization was also partially attenuated by N(omega)-nitro-L-arginine methyl ester (L-NAME) or 1H:-[1,2,4]oxadiazolo[4,3-a]quinoxalin-l-one (ODQ). 4. In phenylephrine-contracted aortic rings, both agonists of K(+) channels, NS1619 and pinacidil, induced greater relaxations and re-polarizations in the preparations obtained from endotoxaemic rats. The NS1619-induced relaxation and re-polarization in arteries from endotoxaemic rats were partially inhibited by tetraethylammonium and completely inhibited by charybdotoxin, L-NAME or ODQ, but not significantly affected by apamin. Similarly, the greater relaxation and re-polarization induced by pinacidil in arteries from endotoxaemic rats were also inhibited by glibenclamide, L-NAME or ODQ. However, these inhibitors had no significant effect on relaxations and re-polarizations induced by NS1619 and pinacidil in arteries from controls. 5. This study provides the electrophysiological and functional evidence showing an abnormal activation of K(+) channels in vascular smooth muscle in animals with endotoxic shock. Our observations suggest that overproduction of nitric oxide causes an activation of large conductance Ca(2+)-activated K(+) channels and ATP-sensitive K(+) channels which contributes to endotoxin-mediated vascular hyporeactivity.

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