title: Effects of atorvastatin and losartan on monocrotaline-induced pulmonary artery remodeling in rats.
abstract: Structural remodeling of pulmonary artery plays an important role in maintaining sustained pulmonary arterial hypertension (PAH). The anti-remodeling effects of statins have been reported in systemic hypertension. In this study, we studied the effects of atovastatin (Ato) or losartan (Los) in monocrotaline (MCL)-induced pulmonary artery remodeling using a rat model. Forty Sprague-Dawley (SD) rats were randomly assigned into four groups (n = 10): normal control (Ctr), PAH, PAH treated with Los, and PAH treated with Ato. We found that in the Los- or Ato-treated group, the mean pulmonary arterial pressure, right heart hypertrophy index, ratio of wall/lumen thickness (WT%), as well as the wall/lumen area (WA%) were significantly reduced compared to the PAH group. Also in pulmonary arteries dissected from rats in the Ato- or Los-treated group, in both mRNA and protein levels, the expression of α1C subunit of voltage-gated calcium channel (Ca(v)α1c) was downregulated, while sarcoplasmic/endoplasmic reticulum calcium-ATPase (SERCA-2a) and inositol 1,4,5 triphosphate receptor 1 (IP3R-1) upregulated. However, the mRNA level of RyR-3 subunit of calcium regulating channel was increased, whereas its protein level was reduced in the treated groups. Our results suggest that atorvastatin or losartan may regress the remodeling of the pulmonary artery in pulmonary hypertensive rats, with differential expression of calcium regulating channels.
authors.affiliation: Fujian Hypertension Research Institute, Department of Internal Medicine, First Affiliated Hospital of Fujian Medical University, Fuzhou, PR China. ldxie@hotmail.com
authors.forename: Liangdi
authors.initials: L
authors.lastname: Xie
authors.forename: Peisen
authors.initials: P
authors.lastname: Lin
authors.forename: Hong
authors.initials: H
authors.lastname: Xie
authors.forename: Changsheng
authors.initials: C
authors.lastname: Xu
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000473:pathology; D000069059:Atorvastatin; D001483:Base Sequence; D020746:Calcium Channels, L-Type / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D016686:Monocrotaline / Q000633:toxicity; D011651:Pulmonary Artery / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D011758:Pyrroles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D020746:Calcium Channels, L-Type; D017931:DNA Primers; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053496:Inositol 1,4,5-Trisphosphate Receptors; C419385:L-type calcium channel alpha(1C); D011758:Pyrroles; D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel; D016686:Monocrotaline; D000069059:Atorvastatin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019808:Losartan