| 17229879 |
Bolognesi M, Sacerdoti D, Piva A, Di Pascoli M, Zampieri F, Quarta S, Motterlini R, Angeli P, Merkel C, Gatta A: Carbon monoxide-mediated activation of large-conductance calcium-activated potassium channels contributes to mesenteric vasodilatation in cirrhotic rats. J Pharmacol Exp Ther. 2007 Apr;321(1):187-94. Epub 2007 Jan 17.
Large-conductance calcium-activated potassium channels (BK (Ca) s) are important regulators of arterial tone and represent a mediator of the endogenous vasodilator carbon monoxide (CO). Because an up-regulation of the heme oxygenase (HO)/CO system has been associated with mesenteric vasodilatation of cirrhosis, we analyzed the interactions of BK (Ca) and of HO/CO in the endothelium-dependent dilatation of mesenteric arteries in ascitic cirrhotic rats. In pressurized mesenteric arteries (diameter, 170-350 microm) of ascitic cirrhotic rats, we evaluated the effect of inhibition of BK (Ca), HO, and guanylyl-cyclase on dilatation induced by acetylcholine and by exogenous CO; and HO-1 and BK (Ca) subunit protein expression. Inhibition of HO and of BK (Ca) reduced acetylcholine-induced vasodilatation more in cirrhotic rats than in control rats, whereas inhibition of guanylyl-cyclase had a similar effect in the two groups. CO was more effective in cirrhotic rats than in control rats, and the effect was hindered by BK (Ca) inhibition. The expression of HO-1 and of BK (Ca) alpha-subunit was higher in mesenteric arteries of cirrhotic rats compared with that of control animals, whereas the expression of the BK (Ca) beta1-subunit was lower. In conclusion, an overexpression of BK (Ca) alpha-subunits, possibly due to HO up-regulation with increased CO production, participates in the endothelium-dependent alterations and mesenteric arterial vasodilatation of ascitic cirrhotic rats. |
2(0,0,0,2) |