title: Combination of sildenafil and simvastatin ameliorates monocrotaline-induced pulmonary hypertension in rats.
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.
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital and Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China.
authors.forename: Tuguang
authors.initials: T
authors.lastname: Kuang
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Baosen
authors.initials: B
authors.lastname: Pang
authors.forename: Xiuxia
authors.initials: X
authors.lastname: Huang
authors.forename: Elyssa D
authors.initials: ED
authors.lastname: Burg
authors.forename: Jason X-J
authors.initials: JX
authors.lastname: Yuan
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D016686:Monocrotaline; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D013450:Sulfones / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000924:Anticholesteremic Agents; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D016686:Monocrotaline; D019821:Simvastatin; D000068677:Sildenafil Citrate