Combined effects of irbesartan and carvedilol on expression of tissue factor and tissue factor pathway inhibitor in rats after myocardial infarction.

The objective of this study was to investigate the effects of irbesartan, carvedilol, and irbesartan plus carvedilol on the expression of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) mRNA and protein in rat myocardium after myocardial infarction (MI). MI was induced in male Wistar rats by ligation of the anterior descending branch of the left coronary artery. Irbesartan at 50 mg/kg/day, carvedilol at 1 mg/kg/day, irbesartan plus carvedilol, or placebo was administered intragastrically; expression of TF and TFPI mRNA and protein was determined by RT-PCR and Western blot analysis. The relative left ventricle weights were lower in all three treatment groups than in the placebo group, with the lowest relative weight in the irbesartan plus carvedilol group (P < 0.001). The size of the infarcted area was lower in the carvedilol and the combined groups than in the placebo group (P < 0.001). The levels of expression of TF and TFPI mRNA and protein were lower in the combined group than in the placebo group or the carvedilol group (P < 0.001). Treatment with irbesartan plus carvedilol reduced the expression of TF and TFPI mRNA and protein after MI in rats, and combined treatment with both agents had greater effects than the single agents alone. These findings suggest that the beneficial effects of these drugs may include anticoagulation and that combined therapy with both agents is an option that should be evaluated further.