Thyroid hormone analog, DITPA, improves endothelial nitric oxide and beta-adrenergic mediated vasorelaxation after myocardial infarction

This study was designed to determine if the thyroid hormone analog 3,5 diiodothyropropionic acid (DITPA), now in clinical trials for heart failure, alters endothelial function after myocardial infarction (MI). Three weeks after MI, adult Sprague-Dawley rats were randomly assigned to DITPA (375 mug/100 g subcutaneous) or no treatment of 3 weeks. In MI rats, left ventricular (LV) end-diastolic pressure and LV dP/dt decreased (P < 0.05). DITPA did not change MAP (87 +/- 10 versus 90 +/- 7 mm Hg) or LV end-diastolic pressure (23 3 versus 19 9 turn Hg) but did lower (P < 0.05) LV dP/dt (4633 +/- 797 versus 3650 +/- 1236 mm Hg/s). In aortic segments from MI rats, DITPA enhanced the acetylcholine dependent vasorelaxation (59 11% at 10(-4) M, P < 0.05) and isoproterenol induced vasorelaxation (57 +/- 13% at 10(-4) M, P < 0.05). The increases in vasorelaxation were blocked with L-NAME and restored with L-arginine. Treatment with DITPA increased (P < 0.05) eNOS protein content in aortic tissue from sham rats (3.8 +/- 12.8 to 44.5 +/- 7.1 integrated intensity units (II)/mug) and in MI rats (5.3 3.4 to 28.3 +/- 8.9 II/mug). In endothelial cells, 24 hours' treatment with DITPA (10 muM) increased (P < 0.01) eNOS protein expression from 22.1 +/- 4.8 to 52.7 +/- 16.8 II/mug protein and DITPA (20 muM) increased eNOS to 49.1 +/- 15.2 II/mug protein. The thyroid analog DITPA enhances endothelial nitric oxide and beta-adrenergic-mediated vasorelaxation by increasing nitric oxide in the vasculature.