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Rosuvastatin attenuates monocrotaline-induced pulmonary hypertension via regulation of Akt/eNOS signaling and asymmetric dimethylarginine metabolism
- Source :
-
European Journal of Pharmacology . Sep2011, Vol. 666 Issue 1-3, p165-172. 8p. - Publication Year :
- 2011
-
Abstract
- 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 (60mg/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. 28days 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 14days and 28days) 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. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 00142999
- Volume :
- 666
- Issue :
- 1-3
- Database :
- Academic Search Index
- Journal :
- European Journal of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 62273603
- Full Text :
- https://doi.org/10.1016/j.ejphar.2011.05.035