Sarcoplasmic reticulum Ca2+ pumps in heart and diaphragm of cardiomyopathic hamster: effects of perindopril.

Abstract

The polymyopathy of the Syrian hamster is associated with alterations of cellular calcium regulation and contractile performance of cardiac and skeletal muscles and, in particular, the diaphragm. Angiotensin-converting enzyme (ACE) inhibitors have been shown to preserve contractile performance. Therefore we analyzed the expression of the genes coding for the sarco(endo)plasmic reticulum Ca(2+)-adenosinetriphosphatase (SERCA) in heart and diaphragm of the cardiomyopathic Syrian hamster (CSH) from the dilated strain Bio 53-58, and we tested the influence of ACE inhibition on accumulation of the different SERCA mRNAs. In the diaphragm of healthy hamsters, two SERCA mRNA isoforms were present: SERCA 1 and SERCA 2. At 6 mo of age, the myopathic process resulted in decreased levels of SERCA 1, whereas the level of SERCA 2 was unchanged. The ACE inhibitor perindopril (1 mg.kg-1.day-1), administered by force feeding from 1 to 6 mo of age, had no effect on the SERCA 1 mRNA level. In heart, the myopathy was associated with a depressed level of SERCA 2 mRNA in 9- but not in 6-mo-old animals. Perindopril treatment from 6 to 9 mo reversed cardiac hypertrophy and the relative decrease in SERCA 2 mRNA level. Preventive treatment with perindopril from 1 to 9 mo tended to prevent (not significantly) the development of cardiac hypertrophy and reduction in SERCA gene expression. In conclusion, the myopathic process affects SERCA gene expression in the diaphragm and subsequently in the heart. Perindopril treatment can prevent SERCA mRNA loss in heart but not in diaphragm.