AT1-receptor blockade enhances ischemic preconditioning in hypertrophied rat myocardium.
The purpose of this study was to determine whether ischemic preconditioning protects contractile function in hypertrophied rat myocardium from ischemia-reperfusion (I/R) injury. Male salt-sensitive rats were fed a high-salt diet for 2 wk to induce myocardial hypertrophy. Nonhypertrophied hearts were obtained from age-matched Sprague-Dawley (SD) rats fed a regular diet. Heart weight-to-body weight ratios were higher in salt-sensitive rats than in SD rats (6.9 +/- 0.2 vs. 4.7 +/- 0.2 g/kg, P < 0.01). A second group of salt-sensitive and SD rats was administered losartan (10 mg. kg(-1). day(-1)), an AT(1)-receptor blocker, for 1 wk before the study. Isolated hearts were preconditioned with transient ischemia before global I/R. After I/R, preconditioned hypertrophied hearts exhibited greater recovery of left ventricular developed pressure compared with that of preconditioned normal hearts (73 +/- 8 vs. 18 +/- 8%, P < 0.01). Left ventricular developed pressure was further enhanced by losartan in both hypertrophied and normal myocardium (99 +/- 5 vs. 73 +/- 8%, P < 0.05 and 97 +/- 15 vs. 18 +/- 8%, P < 0.01). Hypertrophied rat myocardium can be protected from I/R-induced contractile dysfunction by ischemic preconditioning. Losartan improves the ischemic tolerance of normal and hypertrophied myocardium.
Butler
K L
KL
Department of Surgery, Morehouse School of Medicine, Atlanta, Georgia 30310, USA. butlerk@msm.edu
Huang
A H
AH
Gwathmey
J K
JK
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D006332:Cardiomegaly / Q000503:physiopathology*; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D019194:Ischemic Preconditioning / Q000379:methods*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D009929:Organ Size; D051381:Rats; D020303:Rats, Inbred Dahl; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012982:Sodium, Dietary; D016277:Ventricular Function, Left / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012982:Sodium, Dietary; D019808:Losartan