Aliskiren reduces portal pressure in portal hypertensive rats

Ching Chih Chang, Wen Shin Lee, Hui Chun Huang, Fa Yauh Lee*, Sun Sang Wang, Han Chieh Lin, Jing Yi Nong, Shou Dong Lee

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Background Aliskiren is a direct renin inhibitor used in the treatment for arterial hypertension. It can also augment nitric oxide (NO) production, which plays a crucial role in the pathogenesis of portal hypertension and modulation of porto-systemic collaterals. This study investigated the effects of aliskiren on portal pressure and porto-systemic collaterals of portal vein-ligated (PVL) rats. Materials and methods Sham-operated and PVL rats received aliskiren (50mg/kg per day) or distilled water (control) treatment for 10days. The mean arterial pressure and portal pressure were measured by catheterization of the right femoral artery and mesenteric vein, while the superior mesenteric arterial blood flow was measured by Doppler technique. The left adrenal vein and superior mesentery artery were dissected for mRNA study. The PVL rats also underwent preincubation with (i) Krebs solution (control); (ii) 10 -4M aliskiren; or (iii) 10 -4M aliskiren plus nonselective NO inhibitor N ω-nitro-l-arginine (10 -4M), followed by the addition of arginine vasopressin (AVP) to evaluate the collateral vascular responsiveness. Results Aliskiren had systemic arterial pressure- and portal pressure-lowering effects in PVL rats. Superior mesentery arterial resistance also decreased. The constitutive NO synthase was enhanced in the left adrenal vein and superior mesentery artery after aliskiren treatment. Aliskiren attenuated the collateral vasoconstrictive effects of AVP, but the vasodilatory effects were abolished after nonselective NO synthase inhibition. Conclusions Chronic aliskiren use reduces portal pressure in portal hypertensive rats partly due to the modulation of splanchnic and collateral NO synthase.

Original languageEnglish
Pages (from-to)526-533
Number of pages8
JournalEuropean Journal of Clinical Investigation
Volume42
Issue number5
DOIs
StatePublished - May 2012

Keywords

  • Aliskiren
  • Nitric oxide
  • Portal hypertension
  • Porto-systemic collaterals

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