Effect of angiotensin-converting enzyme inhibition on protein kinase C andSR proteins in heart failure

We tested the hypothesis that activation of protein kinase C (PKC) isoforms in pressure-overload heart failure was prevented by angiotensin-converting enzyme (ACE) inhibition, resulting in normalization of cardiac sarcoplasmi c reticulum (SR) Ca2+ ATPase (SERCA) 2a and phospholamban protein levels an d improvement in intracellular Ca2+ handling. Aortic-banded and control gui nea pigs were given ramipril (5 mg . kg(-1). day(-1)) or placebo for 8 wk. Ramipril-treated banded animals had lower left ventricular (LV) and lung we ight, improved survival, increased isovolumic LV mechanics, and improved ca rdiomyocyte Ca2+ transients compared with placebo-treated banded animals. T his was associated with maintenance of SERCA2a and phospholamban protein ex pression. Translocation of PKC-alpha and -epsilon was increased in placebo- treated banded guinea pigs compared with controls and was attenuated signif icantly by treatment with ramipril. We conclude that ACE inhibition attenua tes PKC translocation and prevents downregulation of Ca2+ cycling protein e xpression in pressure-overload hypertrophy. This represents a mechanism for the beneficial effects of this therapy on LV function and survival in hear t failure.