Objective: Cardiac hypertrophy due to pressure overload is associated with several cellular electrophysiological alterations such as prolongation of action potential duration (APD), decrease in transient outward current (I(to)) and occurrence of the pacemaker current I(f). These alterations may play a role in sudden arrhythmic death, which is a major risk factor in myocardial hypertrophy and failure. Since angiotensin II is a key signal for myocyte hypertrophy, we tested if an 8-week treatment of old spontaneously hypertensive rats (SHR) with the antagonist of type-1 angiotensin II receptor (AT1), losartan (10 mg/kg/day), was able to influence the cellular electrophysiologic remodeling associated with cardiac hypertrophy. Methods: Left ventricular myocytes were isolated from control (CTR) or losartan-treated (LOS) 18-month old SHR. Patch-clamped LVM were superfused with a normal Tyrode's solution (to measure action potential) or appropriately modified Tyrode's solution (to measure I(to) and I(f)). Results: Heart weight to body weight ratio (HW/BW) was significantly smaller in LOS (5.69±0.25 mg/g) than in CTR rats (6.67±0.37 mg/g; P1 receptor blockade with losartan prevents the development of myocyte hypertrophy and associated electrophysiological alterations in old SHR. Copyright (C) 2000 Elsevier Science B.V.
- Membrane currents
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine