Prevention of hypertension is associated with reduced susceptibility to histamine-induced arrhythmias in SHR.

Two groups of spontaneously hypertensive rats (SHR) were treated with alpha-methyldopa (2.5 g/L in drinking water) for 12-17 weeks. One group was treated during the normal time course for development of hypertension and myocardial hypertrophy (beginning at age 4 weeks), while the other was treated after stabilization of hypertension/hypertrophy (21 weeks). Appropriate age-matched controls (WKY strain) also were treated. Intracellular microelectrodes were used to monitor action potential configuration, automaticity, and the incidence of arrhythmias (including delayed afterdepolarizations and repetitive tachyarrhythmias) in isolated left ventricles from each group. The younger rats did not develop hypertension of left ventricular hypertrophy; susceptibility of isolated left ventricles to histamine-induced (10(-5) M) arrhythmogenesis was significantly reduced. The older rats showed decreased blood pressure, although not to normal levels; further left ventricular hypertrophy was prevented, though the existing enlargement did not regress. These hearts were as susceptible to the development of histamine-induced arrhythmias as were hearts of untreated SHR. Enhanced susceptibility to arrhythmias in hypertrophied hearts reflects a preventable alteration of the myocardial cell membrane that occurs during the course of blood pressure elevation. This change may be associated with defective sarcolemmal calcium transport in hypertrophied myocardium.