Cardiac hypertrophy induced by prostaglandin F_(2#alpha#) may be mediated by calcineurin signal transduction pathway in rats
Jiang Qingsong, Huang Xienan, Yang Guizhong, Dai Zhikai, Zhou Qixin, Shi Jingshan, Wu Qin
Department of Pharmacology, Zunyi Medical College.Zunyi 563003,Guizhou;China
Abstract
In this paper, we studied the relationship between the prostaglandin F_(2#alpha#) (PGF_(2#alpha#))-induced cardiac hypertrophy and calcineurin (CaN) signal transduction pathway in vivo and in vitro. Male Sprague-Dawley rats were given a single i.p. injection with monocrotaline (MCT) (60 mg/kg) and then given orally with celecoxib (20 mg/kg) or vehicle once a day for 14 d before (from d 1 to d 14) or after (from d 15 to d 28) right ventricular hypertrophy (RVH) was formed. Body weight (BW), right ventricular weight (RV), left ventricular with septum weight (LV), as well as lung weight were determined. RVH index (RVHI=RV/LV), RV/BW, and lung weight/BW were calculated and histological changes were observed with transmission electron microscope. PGF_(2#alpha#) level, atrial natriuretic peptide (ANP) and CaN mRNA expressions, expression of CaN and its downstream effectors, NFAT_(3) and GATA_(4) protein were assayed by EIA kit, RT-PCR, and Western blotting, respectively. The cardiomyocyte hypertrophy in primary culture induced by PGF_(2#alpha#) (0.1 #mu#mol/L) was evaluated by measuring the cell diameter, protein content, and ANP mRNA as well as CaN mRNA expressions. It was found that 14 d or 28 d after MCT was given, the RVHI, RV/BW, and lung weight/BW were significantly increased by 47%, 53% and 118%, and by 64%, 94% and 156%, respectively; at the same time PGF_(2#alpha#) levels in RV tissue were increased by 44% and by 51% with increasing RVHI, and elevated expressions of ANP and CaN mRNA, as well as CaN, NFAT_(3) and GATA_(4) proteins in a positive correlation manner. Furthermore, some histological injuries were found in RV tissue. Celecoxib, a cyclooxygenase inhibitor, obviously blunted the elevation of RVHI, RV/BW, and lung weight/BW no matter it was given before or after RVH. In vitro experiments showed that 0.1 #mu#mol/L PGF_(2#alpha#) significantly increased the cardiomyocyte diameter and protein content, and promoted ANP and CaN mRNA expressions, which was blocked by cyclosporin A, a CaN inhibitor. Our results indicate that PGF_(2#alpha#) may be involved in cardiac hypertrophy induced by MCT in rats through CaN signal transduction pathway.
Key words: Prostaglandin F_(2#alpha#);Cardiac hypertrophy;calcineurin;Monocrotaline
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Citing This Article:
Jiang Qingsong, Huang Xienan, Yang Guizhong, Dai Zhikai, Zhou Qixin, Shi Jingshan, Wu Qin. Cardiac hypertrophy induced by prostaglandin F_(2#alpha#) may be mediated by calcineurin signal transduction pathway in rats . Acta Physiol Sin 2005; 57 (6): (in Chinese with English abstract).