Altered control of vascular tone by adenosine triphosphate-sensitive potassium channels in rats with cirrhosis

Gastroenterology. 1994 Apr;106(4):1016-23. doi: 10.1016/0016-5085(94)90762-5.


Background/aims: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology*
  • Animals
  • Antihypertensive Agents / pharmacology
  • Blood Pressure / drug effects
  • Glyburide / pharmacology
  • Hemodynamics / drug effects
  • Liver Circulation / drug effects
  • Liver Cirrhosis, Experimental / metabolism
  • Liver Cirrhosis, Experimental / physiopathology*
  • Male
  • Picolines / pharmacology
  • Portal System / drug effects
  • Potassium Channels / drug effects*
  • Potassium Channels / physiology*
  • Pyrans / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Splanchnic Circulation / drug effects
  • Vascular Resistance / drug effects
  • Vasomotor System / physiopathology*


  • Antihypertensive Agents
  • Picolines
  • Potassium Channels
  • Pyrans
  • aprikalim
  • Adenosine Triphosphate
  • Glyburide