AHEART December 46/6

Butler, Karyn L., Alice H. Huang, and Judith K. Gwathmey. AT1-receptor blockade enhances ischemic preconditioning in hypertrophied rat myocardium. Am. J. Physiol. 277 (Heart Circ. Physiol. 46): H2482–H2487, 1999.—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 6 0.2 vs. 4.7 6 0.2 g/kg, P , 0.01). A second group of salt-sensitive and SD rats was administered losartan (10 mg·kg21 ·day21), an AT1-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 6 8 vs. 18 6 8%, P , 0.01). Left ventricular developed pressure was further enhanced by losartan in both hypertrophied and normal myocardium (99 6 5 vs. 73 6 8%, P , 0.05 and 97 6 15 vs. 18 6 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.