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Increased phosphodiesterase-5 expression is involved in the decreased vasodilator response to nitric oxide in

Mauricio R Loureiro-Silva1, Yasuko Iwakiri, Juan G Abraldes

  • 1Hepatic Hemodynamic Laboratory, VA Medical Center, West Haven, CT 06516, USA.

Journal of Hepatology
|March 21, 2006
PubMed
Abstract

Insights

Cirrhotic livers show a reduced response to nitric oxide (NO) due to increased phosphodiesterase-5 (PDE-5) expression. Sildenafil citrate reversed this deficiency, restoring NO

Area of Science:

  • Hepatology
  • Vascular Biology
  • Pharmacology

Background:

  • Cirrhotic livers exhibit impaired vasodilator response to nitric oxide (NO).
  • Nitric oxide's effect is modulated by phosphodiesterases, specifically phosphodiesterase-5 (PDE-5), which degrades its second messenger.
  • Understanding PDE-5's role is crucial for addressing vascular dysfunction in liver cirrhosis.

Purpose of the Study:

  • To investigate phosphodiesterase-5 (PDE-5) expression in normal versus cirrhotic rat livers.
  • To pinpoint the location of the diminished nitric oxide (NO) response in cirrhotic livers.
  • To evaluate the efficacy of the PDE-5 inhibitor Sildenafil citrate in restoring NO-mediated vasodilation.

Main Methods:

  • Liver perfusion studies were conducted on normal and cirrhotic rats.
  • Concentration-response curves to a nitric oxide (NO) donor were generated before and after PDE-5 inhibition with Sildenafil.
  • Vascular pressures were continuously monitored throughout the perfusion experiments.

Main Results:

  • Phosphodiesterase-5 (PDE-5) expression was significantly higher in cirrhotic rat livers compared to normal livers.
  • Cirrhotic livers demonstrated a reduced vasodilator response to nitric oxide (NO) in the pre-sinusoidal vasculature.
  • Administration of Sildenafil citrate normalized the vascular response to nitric oxide (NO) in both normal and cirrhotic livers.

Conclusions:

  • Elevated phosphodiesterase-5 (PDE-5) expression contributes to the impaired nitric oxide (NO) vascular response in liver cirrhosis.
  • Targeting PDE-5 with inhibitors like Sildenafil may represent a therapeutic strategy for liver cirrhosis-associated vascular dysfunction.

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