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

Abstract

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.

<b>Downregulation of Peroxisme Proliferator Activated Receptor Gamma Co-Activator 1&alpha; in Diabetic Rats</b>

“…The dosage of 20 mg/kg orally once a day in this study was based on that used in a previous study. 27) Fourth, we did not measure blood pressure in the diabetic rats. Thus, we do not know whether losartan (20 mg/kg orally once a day) would lower the blood pressure in diabetic rats.…”

“…13,14) Therefore, the results of this and recent studies 13,14,17) support the hypothesis that diabetic cardiomyopathy, which is an altered cardiac phenotype independent of coronary atherosclerosis, is a metabolic disturbance resulting in downregulation of cardiac mitochondrial metabolism and biogenesis. [12][13][14] Although the impact of angiotensin II type I (AT1) receptor blocker therapy on improving CHF, LV function, and clinical outcomes has been consistently demonstrated in various clinical settings, [23][24][25][26][27][28][29] the mechanism of action through which these drugs improve CHF and LV function has not been fully elucidated. 27,30,31) The primary finding in this study was that the losartan and not the simvastatin therapy significantly enhanced the PGC-1α gene expression and improved LV function.…”

“…[12][13][14] Although the impact of angiotensin II type I (AT1) receptor blocker therapy on improving CHF, LV function, and clinical outcomes has been consistently demonstrated in various clinical settings, [23][24][25][26][27][28][29] the mechanism of action through which these drugs improve CHF and LV function has not been fully elucidated. 27,30,31) The primary finding in this study was that the losartan and not the simvastatin therapy significantly enhanced the PGC-1α gene expression and improved LV function. Two recent studies 32,33) reported that some AT1 receptor blockers may act as partial agonists of peroxisome proliferator activated receptor-γ.…”

Titin Isoform Switch in Ischemic Human Heart Disease

“…17 Sham-operated controls were treated likewise, except that the suture around the coronary artery was not closed. Animals were euthanized 12 and 24 weeks after ligation.…”

“…Nonnecrotic RV tissue was examined in rats 12 and 24 weeks after surgery 17 and in sham-operated rats. The severity of the chronic disease induced was indicated, eg, by increased LV diameters and RV weightto-body weight ratios ( Figure 6, top right).…”