title: Rosuvastatin attenuates monocrotaline-induced pulmonary hypertension via regulation of Akt/eNOS signaling and asymmetric dimethylarginine metabolism.
abstract: This study was designed to investigate whether rosuvastatin could attenuate monocrotaline-induced pulmonary hypertension via regulation of Akt/eNOS signaling pathway and asymmetric dimethylarginine (ADMA) metabolism in rats. After a single-dose injection of monocrotaline (60 mg/kg), oral administration of rosuvastatin (5mg/kg) was started from day 1 to day 28 (preventive administration) or from day 15 to day 28 (therapeutic administration), or with vehicle as corresponding controls. 28 days after monocrotaline, significant pulmonary hypertension characterized by pulmonary arterial medial wall thickening, right ventricular hypertrophy and right heart failure was observed. Rosuvastatin (5mg/kg, for 14 days and 28 days) treatment significantly attenuated monocrotaline-induced pulmonary vascular remodeling, right ventricular hypertrophy and dysfunction, and normalized the down-regulated pulmonary Akt/p-Akt and eNOS/p-eNOS expressions, while increased DDAH2 expression accompanied by decreased serum level of ADMA. However expression of PRMT1 and GSK3β/p-GSK3β did not differ among all groups (all P>0.05). We concluded that rosuvastatin inhibits monocrotaline-induced pulmonary hypertension through normalization of Akt, eNOS and DDAH2 expressions, and decreasing the level of ADMA.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Ningxia Medical University, PR China.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Pei
authors.forename: Ping
authors.initials: P
authors.lastname: Ma
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Zheng
authors.forename: Lin
authors.initials: L
authors.lastname: Yan
authors.forename: Qingbin
authors.initials: Q
authors.lastname: Xu
authors.forename: Guidong
authors.initials: G
authors.lastname: Dai
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006321:Heart / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D016686:Monocrotaline / Q000494:pharmacology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068718:Rosuvastatin Calcium; D015398:Signal Transduction / Q000187:drug effects*; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018497:Ventricular Dysfunction, Right / Q000188:drug therapy
chemical_list: D015415:Biomarkers; D005464:Fluorobenzenes; D011743:Pyrimidines; D013449:Sulfonamides; C487735:dimethylarginine; D016686:Monocrotaline; D000068718:Rosuvastatin Calcium; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; C541817:PRMT1 protein, rat; D011484:Protein-Arginine N-Methyltransferases; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D000581:Amidohydrolases; C059999:dimethylargininase