Modulation of myocardial sarcoplasmic reticulum Ca++-ATPase in cardiac hypertrophy by angiotensin converting enzyme?

摘要: Myocardial hypertrophy in response to hemodynamic overload is an established risk factor for cardiovascular morbidity and mortality. Partially, this may be due alterations cardiac gene expression, resulting a more fetal-like myocyte phenotype with fragile Ca++-homeostasis. Depressed expression of the sarcoplasmic reticulum Ca++-ATPase hallmark phenotype, contributing prolonged cytosolic Ca++-transients, disturbed diastolic relaxation, altered force-frequency relation, probably, electrophysiologic instability susceptibility malignant arrhythmias. Since angiotensin II growth-promoting several cellular systems, local formation within myocardium might contribute trophic shift overloaded myocardium. Several observations are consistent hypothesis: ACE angiotensinogen enhanced experimental myocardial human endstage congestive heart failure; hypertrophy-induced putative normalisation systolic wall stress demonstrated renormalization ventricular tissue activity activity; normalizing by chronic nonhypotensive inhibitor therapy caused parallel partial normalization underexpression CA++-ATPase. This Ca++-homeostasis ACE-inhibition attenuated concomitant application bradykinin-2 receptor blockade, indicating involvement bradykinin metabolism modulation inhibition. While these direct influence on sarcolasmic reticulum, cell type specific mechanism unknown.