Combination of sildenafil and simvastatin ameliorates monocrotaline-induced pulmonary hypertension in rats

Tuguang Kuang, Jun Wang, Baosen Pang, Xiuxia Huang, Elyssa D. Burg, Jason X.J. Yuan, Chen Wang

Research output: Contribution to journalArticle

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)456-464
Number of pages9
JournalPulmonary Pharmacology and Therapeutics
Volume23
Issue number5
DOIs
StatePublished - Oct 1 2010
Externally publishedYes

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Keywords

  • Monocrotaline
  • Pulmonary arterial hypertension
  • Sildenafil
  • Simvastatin
  • Vascular remodeling

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Biochemistry, medical
  • Pharmacology (medical)

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