Losartan prevents contractile dysfunction in rat myocardium after left ventricular myocardial infarction

We studied the effects of chronic losartan (Los) treatment on contractile f unction of isolated right ventricular (RV) trabeculae from rat hearts 12 wk after left ventricular (LV) myocardial infarction (MI) had been induced by ligation of the left anterior descending artery at 4 wk of age. After reco very, one-half of the animals were started on Los treatment (MI+Los; 30 mg. kg(-1).day(-1) per os); the remaining animals were not treated (MI group). Rats without infarction or Los treatment served as controls (Con group). MI resulted in increases in LV and RV weight and unstressed LV cavity diamete r; these were partially prevented by Los treatment. The active peak twitch force-sarcomere length relation was depressed in MI compared with either Co n or MI+Los. Likewise, maximum Ca2+ saturated twitch force was depressed in MI, whereas twitch relaxation and twitch duration were prolonged. Myofilam ent function, as measured in skinned trabeculae, was not significantly diff erent among the Con, MI, and MI+Los groups. We conclude that Los prevents c ontractile dysfunction in rat RV trabeculae after LV MI. Our results sugges t that the beneficiary effect of Los treatment results not from improved my ofilament function but rather from improved myocyte Ca2+ homeostasis.