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Atorvastatin prevents dehydromonocrotaline-induced pulmonary hypertension in beagles.
MedLine Citation:
PMID:  22888849     Owner:  NLM     Status:  In-Data-Review    
ABSTRACT Background: Pulmonary arterial hypertension is a life-threatening disease characterized by marked and sustained elevation of blood pressure in the lungs. Statins, 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase inhibitors, have been shown to attenuate the effects of pulmonary hypertension resulting from hypoxia, Monocrotaline exposure, or Monocrotaline exposure in the setting of pneumonectomy. In particular, the effects of Simvastatin have been well studied. Whether other statins, such as Atorvastatin, are capable of preventing dehydromonocrotaline-induced pulmonary hypertension in beagles has not been explored. Methods: We used eighteen 3-month-old beagles of both genders, weighing 10.3 ± 3.2 kg. The experimental animals were randomized into one of 3 groups: the control group (n = 6), the dehydromonocrotaline (DHMC) + vehicle group (n = 5), and the DHMC + Atorvastatin group (n = 7). The beagles were injected with DHMC (n = 12) on day 1, and from day 5 to day 65 they received Atorvastatin (2 mg/kg, daily by gavage) or vehicle (0.9% saline, daily by gavage) treatment. We used the thermodilution method of hemodynamic measurements at baseline and at day 65 of treatment. At day 65, pulmonary tissue was sampled for morphometry and real-time quantitative PCR. Results: After 65 days, DHMC increased mean pulmonary arterial pressure (mPAP), and this increase was prevented with Atorvastatin treatment (32 ± 11 mmHg vs. 15 ± 3 mmHg, P < .05). Hematoxylin and eosin staining demonstrated less pulmonary endothelium destruction and smooth muscle cell proliferation in the Atorvastatin-treated beagles, compared with the DHMC group. The eNOS mRNA expression was increased in the DHMC group, and this increase was prevented in the Atorvastatin-treated group. In addition, IL-1β, prepro-ET-1, TNF-α, and VEGF (vascular endothelial growth factor) mRNA expression levels were increased in the lungs of the DHMC group, and these increases were reduced toward normal levels in the Atorvastatin-treated group. Conclusion: Atorvastatin prevents the effects of monocrotaline-induced pulmonary hypertension in beagles.
Dandan Chen; Daxin Zhou; Juying Qian; Fadong Chen; Lihua Guan; Lili Dong; Junbo Ge
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Experimental lung research     Volume:  38     ISSN:  1521-0499     ISO Abbreviation:  Exp. Lung Res.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8004944     Medline TA:  Exp Lung Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  333-43     Citation Subset:  IM    
Department of Cardiology, Zhongshan Hospital of Fudan University, Shanghai Cardiovascular Disease Institute, Shanghai, China.
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