Sarcoplasmic reticulum Ca transport and gene expression in congestive heart failure are modified by imidapril treatment
نویسندگان
چکیده
Shao, Qiming, Bin Ren, Harjot K. Saini, Thomas Netticadan, Nobuakira Takeda, and Naranjan S. Dhalla. Sarcoplasmic reticulum Ca transport and gene expression in congestive heart failure are modified by imidapril treatment. Am J Physiol Heart Circ Physiol 288: H1674–H1682, 2005. First published December 2, 2004; doi: 10.1152/ajpheart.00945.2004.—This study was designed to test the hypothesis that blockade of the renin-angiotensin system improves cardiac function in congestive heart failure by preventing changes in gene expression of sarcoplasmic reticulum (SR) proteins. We employed rats with myocardial infarction (MI) to examine effects of an angiotensin-converting enzyme inhibitor, imidapril, on SR Ca transport, protein content, and gene expression. Imidapril (1 mg kg 1 day ) was given for 4 wk starting 3 wk after coronary artery occlusion. Infarcted rats exhibited a fourfold increase in left ventricular end-diastolic pressure, whereas rates of pressure development and decay were decreased by 60 and 55%, respectively. SR Ca uptake and Ca pump ATPase, as well as Ca release and ryanodine receptor binding activities, were depressed in the failing hearts; protein content and mRNA levels for Ca pump ATPase, phospholamban, and ryanodine receptor were also decreased by 55– 65%. Imidapril treatment of infarcted animals improved cardiac performance and attenuated alterations in SR Ca pump and Ca release activities. Changes in protein content and mRNA levels for SR Ca pump ATPase, phospholamban, and ryanodine receptor were also prevented by imidapril treatment. Beneficial effects of imidapril on cardiac function and SR Ca transport were not only seen at different intervals of MI but were also simulated by another angiotensin-converting enzyme inhibitor, enalapril, and an ANG II receptor antagonist, losartan. These results suggest that blockade of the reninangiotensin system may increase the abundance of mRNA for SR proteins and, thus, may prevent the depression in SR Ca transport and improve cardiac function in congestive heart failure due to MI.
منابع مشابه
Sarcoplasmic reticulum Ca2+ transport and gene expression in congestive heart failure are modified by imidapril treatment.
This study was designed to test the hypothesis that blockade of the renin-angiotensin system improves cardiac function in congestive heart failure by preventing changes in gene expression of sarcoplasmic reticulum (SR) proteins. We employed rats with myocardial infarction (MI) to examine effects of an angiotensin-converting enzyme inhibitor, imidapril, on SR Ca(2+) transport, protein content, a...
متن کاملModification of sarcolemmal Na+-K+-ATPase and Na+/Ca2+ exchanger expression in heart failure by blockade of renin-angiotensin system.
The activities of both sarcolemmal (SL) Na(+)-K(+)-ATPase and Na(+)/Ca(2+) exchanger, which maintain the intracellular cation homeostasis, have been shown to be depressed in heart failure due to myocardial infarction (MI). Because the renin-angiotensin system (RAS) is activated in heart failure, this study tested the hypothesis that attenuation of cardiac SL changes in congestive heart failure ...
متن کاملAntiplatelet therapy attenuates subcellular remodelling in congestive heart failure
Antiplatelet agents, sarpogrelate (SAR), a 5-HT(2A) receptor antagonist, and cilostazol (CIL), a phosphodiesterase III (PDE-III) inhibitor, are used for the treatment of peripheral vascular disease. We tested whether these agents affect cardiac function and subcellular remodelling in congestive heart failure (CHF) induced by myocardial infarction (MI). Three weeks after MI, rats were treated da...
متن کاملAlterations in sarcoplasmic reticulum gene expression in human heart failure. A possible mechanism for alterations in systolic and diastolic properties of the failing myocardium.
Recent studies have shown that intracellular Ca2+ handling is abnormal in the myocardium of patients with end-stage heart failure. Muscles from the failing hearts showed a prolonged Ca2+ transient and a diminished capacity to restore a low resting Ca2+ level during diastole. Accordingly, we examined whether this defect in Ca2+ transport function is due to alterations in sarcoplasmic reticulum g...
متن کاملSubcellular remodelling may induce cardiac dysfunction in congestive heart failure.
It is commonly held that cardiac remodelling, represented by changes in muscle mass, size, and shape of the heart, explains the progression of congestive heart failure (CHF). However, this concept does not provide any clear information regarding the development of cardiac dysfunction in CHF. Extensive research has revealed that various subcellular organelles such as the extracellular matrix, sa...
متن کامل