Combination of Sildenafil and Simvastatin Ameliorates Monocrotaline-induced Pulmonary Hypertension in Rats

Overview

Journal Pulm Pharmacol Ther

Specialty Pulmonary Medicine

Date 2010 Mar 2

PMID 20188205

Citations 13

Authors

Tuguang Kuang

Jun Wang

Baosen Pang

Xiuxia Huang

Elyssa D Burg

Jason X-J Yuan

Chen Wang

Affiliations

Soon will be listed here.

Abstract

Sildenafil, a phosphodiesterase-5 inhibitor, and simvastatin, a cholesterol lowering drug, both have therapeutic effects on PAH; however, the combination of these drugs has not been tested in the treatment of PAH. The purpose of this study was to determine whether the combination of sildenafil and simvastatin is superior to each drug alone in the prevention of MCT-induced PAH. Phosphorylated Smad levels were decreased in lung tissue in MCT-injected rats, whereas ERK protein levels were increased. This indicates a possible role for an increase in mitogenic ERK activity in addition to decreased proapoptotic Smad signaling in the MCT model of PAH. Combination sildenafil and simvastatin treatment prevented the MCT-induced increases in right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH), exerted an anti-proliferative effect on pulmonary artery smooth muscle cells (PASMC). Our results indicate that combination therapy with sildenafil and simvastatin attenuated the development of pulmonary hypertension more than either treatment alone.

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