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Inactivation of extrahepatic vascular Akt improves systemic hemodynamics and sodium excretion in cirrhotic rats

G Fernández-Varo1, P Melgar-Lesmes, G Casals

  • 1Biochemistry and Molecular Genetics Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain.

Journal of Hepatology
|August 31, 2010
PubMed
Abstract

Insights

Inactivating vascular Akt improves circulation and kidney function in cirrhotic rats. This targeted approach offers a potential therapeutic strategy for managing complications of cirrhosis and ascites.

Area of Science:

  • Cardiovascular Biology
  • Renal Physiology
  • Molecular Medicine

Background:

  • Cirrhosis and ascites are linked to vascular Akt/eNOS pathway overactivity, impacting hemodynamics and renal function.
  • Intrahepatic Akt/eNOS activity is impaired in cirrhosis, complicating therapeutic strategies.
  • Selective inhibition of vascular eNOS without affecting liver function is a key challenge.

Purpose of the Study:

  • To assess the feasibility of selectively inhibiting vascular eNOS.
  • To determine if endothelial transduction of a constitutively inactive Akt mutant (AA-Akt) improves circulatory function and sodium excretion in cirrhotic rats with ascites.

Main Methods:

  • Adenoviral vectors encoding β-galactosidase (β-gal) or AA-Akt were administered to control and cirrhotic rats.
  • Hemodynamic studies and 24-h urine collection were performed.
  • Tissue samples were analyzed for Akt and eNOS expression.

Main Results:

  • AA-Akt transduction improved systemic hemodynamics, splanchnic perfusion pressure, and renal excretory function.
  • No significant change in portal pressure was observed with AA-Akt.
  • β-gal activity was detected in extrahepatic tissues but not in the cirrhotic liver.

Conclusions:

  • Inactivating extrahepatic vascular Akt ameliorates systemic hemodynamics and renal excretory function in experimental cirrhosis.
  • This approach, involving decreased nitric oxide expression, shows promise for managing cirrhotic complications.
  • Targeting vascular Akt offers a potential therapeutic avenue for cirrhosis with ascites.

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