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_vα1c) 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.

• pulmonary arterial hypertension
• atorvastatin
• losartan
• calcium regulating channels
• remodeling

ACKNOWLEDGMENTS

We thank Mr. Sheng Wu for his assistance in heomdynamic measurements, Yaping Gao for her technical assistance in histologic staining, Ling Lin for microscopic photography, as well as Youqi Huang and Dr. Ye Peng for language polishing.

This research was supported by grants from the Fujian Provincial Natural Science Foundations (No. C0540010 and 2008J0082) and the key program of scientific research of Fujian Medical University (No. 09ZD005).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.