Large-conductance calcium-activated potassium channels modulate vascular tone in experimental cirrhosis

Aina Rodríguez-Vilarrupla1, Mariona Graupera, Vasilica Matei

  • 1Hepatic Hemodynamic Laboratory, Liver Unit, Institut Malalties Digestives i Metabòliques, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Ciberehd, Barcelona, Spain.

Insights

Large-conductance calcium-activated potassium (BK(Ca)) channels are overexpressed in cirrhotic rat livers. This suggests BK(Ca) channels may compensate for increased hepatic vascular tone in cirrhosis.

Area of Science:

  • Physiology
  • Pharmacology
  • Hepatology

Background:

  • Large-conductance calcium-activated potassium (BK(Ca)) channels are key regulators of vascular tone.
  • Activated hepatic stellate cells (HSC) express BK(Ca) channels.
  • Cirrhosis is associated with altered liver vascular tone.

Purpose of the Study:

  • To investigate the role of BK(Ca) channels in regulating vascular tone in normal and cirrhotic rat livers.
  • To assess BK(Ca) channel expression in cirrhotic livers.

Main Methods:

  • Portal perfusion pressure (PP) was measured in response to vasoconstrictors and vasodilators.
  • BK(Ca) channel blockers (Iberiotoxin) and openers (NS1619) were used.
  • BK(Ca) mRNA and protein expression in HSC was quantified.

Main Results:

  • BK(Ca) channel blockade increased baseline PP and exacerbated vasoconstriction in cirrhotic livers.
  • BK(Ca) channel activation had a mild effect on baseline PP but attenuated hyperresponse to vasoconstrictors.
  • Both BK(Ca) mRNA and protein levels were upregulated in cirrhotic livers.

Conclusions:

  • BK(Ca) channels are overexpressed in carbon tetrachloride-induced cirrhosis.
  • Overexpression of BK(Ca) channels may represent a compensatory mechanism against increased hepatic vascular tone in cirrhosis.
Abstract

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