Losartan prevents contractile dysfunction in rat myocardium after left ventricular myocardial infarction.
We studied the effects of chronic losartan (Los) treatment on contractile function 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 recovery, one-half of the animals were started on Los treatment (MI+Los; 30 mg x kg(-1) x 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 diameter; these were partially prevented by Los treatment. The active peak twitch force-sarcomere length relation was depressed in MI compared with either Con or MI+Los. Likewise, maximum Ca2+ saturated twitch force was depressed in MI, whereas twitch relaxation and twitch duration were prolonged. Myofilament function, as measured in skinned trabeculae, was not significantly different among the Con, MI, and MI+Los groups. We conclude that Los prevents contractile dysfunction in rat RV trabeculae after LV MI. Our results suggest that the beneficiary effect of Los treatment results not from improved myofilament function but rather from improved myocyte Ca2+ homeostasis.
Daniëls
M C
MC
Department of Cardiology, Groot Ziekengasthuis, 5200 ME Den Bosch, The Netherlands.
Keller
R S
RS
de Tombe
P P
PP
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002118:Calcium / Q000493:pharmacokinetics; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology; D006706:Homeostasis / Q000187:drug effects; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology*; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects*; D009203:Myocardial Infarction / Q000188:drug therapy / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D012518:Sarcomeres / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D019808:Losartan; D002118:Calcium