Aliskiren reduces portal pressure in portal hypertensive rats.

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 (50 mg/kg per day) or distilled water (control) treatment for 10 days. 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(-4) M aliskiren; or (iii) 10(-4) M aliskiren plus nonselective NO inhibitor N(ω)-nitro-L-arginine (10(-4) M), 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.

• Authors: Ching-Chih Chang, Wen-Shin Lee, Hui-Chun Huang, Fa-Yauh Lee, Sun-Sang Wang, Han-Chieh Lin, Jing-Yi Nong, Shou-Dong Lee
• Journal: European journal of clinical investigation (Eur J Clin Invest) Vol. 42 Issue 5 Pg. 526-33 (May 2012) ISSN: 1365-2362 [Electronic] England
• PMID: 22023532 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.

Chemical References

• Amides
• Antihypertensive Agents
• Fumarates
• Nitric Oxide
• aliskiren
• Nitric Oxide Synthase
• Renin

Topics

• Amides (pharmacology)
• Animals
• Antihypertensive Agents (pharmacology)
• Blood Pressure (drug effects)
• Collateral Circulation (drug effects)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Fumarates (pharmacology)
• Hypertension, Portal (drug therapy)
• Male
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase (metabolism)
• Portal Pressure (drug effects)
• Portal System (drug effects)
• Rats
• Rats, Sprague-Dawley
• Renin (antagonists & inhibitors, pharmacology)