Long-term treatment of spontaneously hypertensive rats with losartan and electrophysiological remodeling of cardiac myocytes

Elisabetta Cerbai, Antonio Crucitti, Laura Sartiani, Petra De Paoli, Roberto Pino, Maria Luisa Rodriguez, Gianfranco Gensini, Alessandro Mugelli

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)388-396
Number of pages9
JournalCardiovascular Research
Volume45
Issue number2
DOIs
Publication statusPublished - Jan 14 2000

Keywords

  • Angiotensin
  • Hypertrophy
  • Membrane currents
  • Myocytes
  • Remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Cerbai, E., Crucitti, A., Sartiani, L., De Paoli, P., Pino, R., Rodriguez, M. L., Gensini, G., & Mugelli, A. (2000). Long-term treatment of spontaneously hypertensive rats with losartan and electrophysiological remodeling of cardiac myocytes. Cardiovascular Research, 45(2), 388-396. https://doi.org/10.1016/S0008-6363(99)00344-2