RESTORATION OF ACTION-POTENTIAL DURATION AND TRANSIENT OUTWARD CURRENT BY REGRESSION OF LEFT-VENTRICULAR HYPERTROPHY

The presence of left ventricular hypertrophy (LVH) is associated with an increased incidence of arrhythmias, Our previous study on hypertrop hied rat hearts has demonstrated that regression of LVH prevents ische mia-induced lethal arrhythmias. To elucidate the underlying mechanism of the reduced incidence of arrhythmias in regression of LVH, we exami ned electrophysiological properties of both hypertrophied and regresse d left ventricular cells. Hearts from spontaneously hypertensive rats (SM) were used as LVH, and those from Wistar-Kpoto rats (WKY) served a s control. SHR with regression of LVH (REG) was produced by captopril treatment. Action potentials and membrane currents of subendocardial l eft ventricular cells were compared by the whole-cell patch-clamp tech niques. Although the membrane capacitance of SHR cells was significant ly greater than that of WKY cells, that of REG cells was normalized to the control level. Prolonged action potential duration (APD) and redu ced density of transient outward current (i(to)) in SHR cells was norm alized by LVH regression (APD at 75% repolarization (ms) and i(to) den sity at + 60 mV (pA/pF): WKY 36.1+/-4.2 11.3 +/- 1.3, SHR 73.1 +/- 12. 9, 5.2 +/- 0.7 dagger, REG 29.5 +/- 3.9, 10.4 +/- 2.0*, P=0.015 dagge r, P=0.001 v WKY). No significant differences were observed in the den sities of steady-state outward current, inward rectifier current, and L-type Ca2+ current. The restoration of i(to) density by regression of LVH could normalize the prolonged APD in hypertensive LVH, which may be causally related to the reduced incidence of arrhythmias in LVH reg ression. (C) 1997 Academic Press Limited.