Chronic inhibition of Na+/H+-exchanger attenuates cardiac hypertrophy and prevents cellular remodeling in heart failure

摘要: Objective : In patients with heart disease, the transition from compensatory hypertrophy to failure (HF) is associated altered calcium handling. Up-regulated Na+/H+-exchanger (NHE-1) activity underlies increased [Na+]i and disturbance of cellular handling in HF. We hypothesize that chronic inhibition NHE-1 prevents hypertrophic response, remodeling, development HF. Methods Rabbits received a control or cariporide (inhibitor NHE-1) diet for 3 months, starting after induction combined volume pressure overload. Age-matched animals served as control. Development HF was examined echocardiographically electrocardiographically months. [Na+]i, [Ca2+]i, pHi, action potentials were measured left ventricular midmural myocytes SBFI, indo-1, SNARF, di-4-anepps. Sarcoplasmic reticulum content calculated response [Ca2+]i rapid cooling. Calcium after-transients elicited by cessation stimulation (3 Hz) presence 100 nmol/l noradrenalin. Results Chronic treatment rabbits specific inhibitor greatly attenuated entirely abolished HF; heart/body weight ratio only little, no change lung occurred, dimensions fractional shortening changed mildly, ascites not present, QT duration did increase, sudden death occur. also prevented electrical ionic remodeling. Myocyte unaltered, prolonged, cytoplasmic sodium SR remained undisturbed, increase incidence after-transient dependent delayed depolarizations (DADs) occurred. Conclusion conclude enhanced cardiac remodeling experimental failure, dietary attenuates hypertrophy, HF,