Nicardipine and cardiac hypertrophy: effects on left ventricular mass. Haemodynamics and mechanical performance in renovascular hypertensive rats

Abstract

Subject objective: The aim was to determine the effects of nicardipine treatment (10-15 mg.kg-1.d-1 intraperitoneal) on left ventricular hypertrophy, coronary haemodynamics, and mechanical performance in renovascular hypertensive rats.

Design: Systemic and coronary haemodynamic variables were evaluated by using microspheres in conscious rats, while mechanical performance and elasticity were measured on isolated papillary muscles from the same animals.

Experimental animals: Male Sprague-Dawley rats, weight 150-180 g, were used. Nine treated rats were compared with control groups, consisting of 9 sham operated, 12 untreated hypertensive, and 9 nephrectomised rats.

Measurements and main results: Eight weeks after clipping, removal of the ischaemic kidney allowed the normalisation of ventricular mass and the reversal of changes induced by hypertrophy except prolongation of timing parameters. Nicardipine administration led to an efficient but incomplete control of blood pressure, which fell from 208(SEM 5) mm Hg in untreated hypertensive rats to 155(4) mm Hg in treated rats, p less than 0.01. After eight weeks of treatment, the reduction in left ventricular mass, from 3.10(0.10) mg.g-1 in untreated rats to 2.72(0.018) mg.g-1 in treated rats was significant (p less than 0.01) but was less than the pressure decrease. In treated hypertensive rats, coronary blood flow was increased and redistributed at rest in favour of the subepicardial layers but was significantly reduced after maximum vasodilatation, to 1.618(0.077) litre.min-1.100 g, in nicardipine treated rats. A reversal of impaired myocardial mechanical indices towards control values was observed except for time to peak force and time to half relaxation.

Conclusions: Nicardipine treatment allowed blood pressure control, reduction of left ventricular mass, and improvement in mechanical performance, but was unable to restore minimal coronary vascular resistance. The results suggest that, although blood pressure decrease is obviously important, it may not be the sole factor in the reversal of cardiac hypertrophy.