Regression of cardiomyocyte hypertrophy in SHR following chronic inhibition of the Na+/H+ exchanger

Objective: Experiments were performed to examine the effect of chronic inhibition of the Na+/H+ exchanger isoform-1 (NHE-1) on cardiac hypertrophy of spontaneously hypertensive rats (SHR). Methods: SHR were orally treated during I month with two different doses (0.3 and 3.0 mg/kg/day) of the NHE-1 inhibitor, cariporide, or nifedipine (10.0 mg/kg/day). Results: The two doses of cariporide did not differ in their effects after I month of treatment, since both induced a slight decrease in systolic blood pressure (SBP) of similar to6 mmHg and regression of the heart weight to body weight ratio (mg/g) from 3.28+/-0.05 to 3.04+/-0.05 (0.3 m-) and 2.99+/-0.10 (3.0 mg P<0.05). Nifedipine, given for the same period, produced similar reduction in the hypertrophy index (3.03+/-0.05), but with a much greater decrease in arterial pressure (35.6+/-7.4 mmHg). Chronic treatment with cariporide induced a complete regression of the augmented cross sectional area of left ventricular myocytes without significant changes in collagen content, serum procollagen I propeptide levels or myocardial distensibility. Conclusions: NHE inhibition represents a novel approach to induce regression of pathological hypertrophy of the heart. The finding can be rationalized mechanistically by previous in vitro studies suggesting a role of the NHE in the development of myocardial hypertrophy. (C) 2002 Elsevier Science BY All rights reserved.