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J Hepatol. 2001 Sep;35(3):350-7.

Role of small-conductance Ca2+-dependent K+ channels in in vitro nitric oxide-mediated aortic hyporeactivity to alpha-adrenergic vasoconstriction in rats with cirrhosis.

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1
Laboratoire d'Hémodynamique Splanchnique et de Biologie Vasculaire, INSERM U-481, Hĵpital Beaujon, Clichy, France.

Abstract

BACKGROUND/AIMS:

In vitro studies have shown that cirrhotic aortas are hyporeactive to the contractile effect of vasoconstrictors because upregulated endothelial nitric oxide-synthase (NOS) overproduces nitric oxide (NO). Although stimulation of endothelial small-conductance Ca2+-dependent K+ (SK(Ca)) channels may elicit vasorelaxation in normal arteries, the role of these channels in cirrhosis-induced hyporeactivity is unknown. Thus, the aim of the present study was to investigate the role of endothelial SK(Ca) channels in cirrhosis-induced, NO-mediated, in vitro aortic hyporeactivity to alpha1-adrenergic vasoconstrictors.

METHODS:

Isolated thoracic aortas from cirrhotic and normal rats were used. The effects of apamin, a selective SK(Ca) channel blocker, were measured on the vascular reactivity to phenylephrine. In addition, SK(Ca) channel protein expression was studied. The effects of iberiotoxin and charybdotoxin, blockers of other K(Ca) channels, were also studied in cirrhotic aortas.

RESULTS:

Apamin suppressed cirrhosis-induced aortic hyporeactivity to phenylephrine in an endothelium-dependent, NOS-inhibitor-sensitive manner. SK(Ca) channel protein was overexpressed in cirrhotic aortic walls. Iberiotoxin abolished cirrhosis-induced aortic hyporeactivity to phenylephrine in an endothelium-dependent but NOS-inhibitor-resistant manner. Charybdotoxin did not induce any significant increase in phenylephrine-elicited contraction.

CONCLUSIONS:

In cirrhotic aortas, the overexpression and overactivity of endothelial SK(Ca) channels contributes to in vitro NO-mediated hyporeactivity to the contractile action of alpha1-adrenergic agonists.

PMID:
11592596
[Indexed for MEDLINE]
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