Altered control of vascular tone by adenosine triphosphate-sensitive potassium channels in rats with cirrhosis.
OBJECTIVE
Because the activation of arterial adenosine triphosphate (ATP)-sensitive potassium (KATP) channels is known to induce vasodilation, these channels may contribute to baseline vasodilator tone in cirrhosis. This study aimed to examine hemodynamic responses to glibenclamide, a KATP channel blocker, and to aprikalim, a vasodilator activating KATP channels, in normal and cirrhotic rats.


METHODS
Splanchnic and systemic hemodynamic responses to glibenclamide (2.5, 5, 20, 30 mg/kg, intravenously) were studied. The arterial pressure response to aprikalim (200 mu/kg, intravenously) was studied with and without glibenclamide pretreatment (20 mg/kg).


RESULTS
In cirrhotic rats, glibenclamide (5, 20, 30 mg/kg but not 2.5 mg/kg) significantly increased vascular resistance in portal and systemic territories. In normal rats, the latter effects occurred with 20 and 30 mg/kg of glibenclamide only. Aprikalim-induced arterial hypotension was significantly less marked in cirrhotic than in normal rats. Following glibenclamide, aprikalim-induced arterial hypotension was significantly less marked in cirrhotic than in normal animals.


CONCLUSIONS
In rats with cirrhosis, the glibenclamide-induced vasoconstriction indicates that a vasodilator tone due to KATP channel opening existed under baseline conditions. Moreover, this study suggests that the control of vascular tone by KATP channels is altered in cirrhosis.
Moreau
R
R
Laboratoire d'Hémodynamique Splanchnique (INSERM U-24), Hôpital Beaujon, Clichy, France.
Komeichi
H
H
Kirstetter
P
P
Ohsuga
M
M
Cailmail
S
S
Lebrec
D
D
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D008102:Liver Circulation / Q000187:drug effects; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D010847:Picolines / Q000494:pharmacology; D011168:Portal System / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D011714:Pyrans / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014666:Vasomotor System / Q000503:physiopathology*
D000959:Antihypertensive Agents; D010847:Picolines; D015221:Potassium Channels; D011714:Pyrans; C061043:aprikalim; D000255:Adenosine Triphosphate; D005905:Glyburide