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 hypertrophied rat hearts has demonstrated that regression of LVH prevents ischemia-induced lethal arrhythmias. To elucidate the underlying mechanism of the reduced incidence of arrhythmias in regression of LVH, we examined electrophysiological properties of both hypertrophied and regressed left ventricular cells. Hearts from spontaneously hypertensive rats (SHR) were used as LVH, and those from Wistar-Kyoto rats (WKY) served as control. SHR with regression of LVH (REG) was produced by captopril treatment. Action potentials and membrane currents of subendocardial left ventricular cells were compared by the whole-cell patch-clamp techniques. Although the membrane capacitance of SHR cells was significantly greater than that of WKY cells, that of REG cells was normalized to the control level. Prolonged action potential duration (APD) and reduced density of transient outward current (ito) in SHR cells was normalized by LVH regression (APD at 75% repolarization (ms) and ito density at +60 mV (pA/pF): WKY 36.1 +/- 4.2, 11.9 +/- 1.3, SHR 73.1 +/- 12.9, 5.2 +/- 0.7, REG 29.5 +/- 3.9, 10.4 +/- 2.0, P = 0.015, P = 0.001 v WKY). No significant differences were observed in the densities of steady-state outward current, inward rectifier current, and L-type Ca2+ current. The restoration of ito 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 regression.
Yokoshiki
H
H
Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Japan.
Kohya
T
T
Tomita
F
F
Tohse
N
N
Nakaya
H
H
Kanno
M
M
Kitabatake
A
A
D000200:Action Potentials; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism; D002216:Captopril / Q000627:therapeutic use; D006321:Heart / Q000502:physiology / Q000503:physiopathology; D006352:Heart Ventricles / Q000166:cytology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D009929:Organ Size; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D016276:Ventricular Function
D000959:Antihypertensive Agents; D002216:Captopril; D002118:Calcium