Diltiazem prevents hypertrophy progression, preserves systolic function, and normalises myocardial oxygen utilisation in the spontaneously hypertensive rat

Abstract

The effects of diltiazem, a calcium channel blocker, and methyldopa, an adrenergic blocker, on left ventricular hypertrophy and left ventricular function were assessed in spontaneously hypertensive rats and Wistar-Kyoto controls. Diltiazem (30 mg·kg^−l/day), methyldopa (400 mg·kg^−l/day), or placebo were given with water for six months. Left ventricular function was studied in 12 month old animals using an isovolumically contracting heart preparation by measuring maximum developed pressure and myocardial oxygen consumption. Systolic blood pressure was reduced by both drugs but more so by methyldopa. Despite its lesser antihypertensive effect, diltiazem reduced heart to body weight ratios in the spontaneously hypertensive rat to a similar degree as methyldopa (3.4(0.2) and 3.4(0.1) compared with placebo 3.7(0.2), pvs 166(11) mmHg, pvs 28.3(3.8) ml·min⁻¹·100 g⁻⁻¹, pvs 24.5(0.6) ml·min⁻¹·100 g^−l pvs the spontaneously hypertensive rat receiving placebo). Diltiazem and methyldopa normalised the isomyosin composition in the spontaneously hypertensive rat. Myocardial concentrations of energy related metabolites obtained at maximum developed pressure were not different between spontaneously hypertensive rats receiving placebo and controls. However, both diltiazem and methyldopa treated spontaneously hypertensive rats showed a significant reduction in adenosine triphosphate and phosphocreatine and a rise in inorganic phosphate. The decrease in adenosine triphosphate was inversely related to developed pressure (r=-0.69, p<0.05), suggesting that after reversal of left ventricular hypertrophy there is an increase in adenosine triphosphate utilisation. Thus, reversal of left ventricular hypertrophy can be accomplished with agents that act by unrelated mechanisms and produce different degrees of blood pressure control. Reversal is associated with an improvement in left ventricular function and normalisation of myocardial oxygen consumption, particularly with diltiazem.