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

Peter H. Spooner, Hoang M. Thai, Steven Goldman, Mohamed A. Gaballa

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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 μg/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 mm Hg) but did lower (P < 0.05) LV dP/dt (4633 ± j_ 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 ± 2.8 to 44.5 ± 7.1 integrated intensity units (II)/μg) and in MI rats (5.3 ± 3.4 to 28.3 ± 8.9 II/μg). In endothelial cells, 24 hours' treatment with DITPA (10 μM) increased (P < 0.01) eNOS protein expression from 22.1 ± 4.8 to 52.7 ± 16.8 II/gg protein and DITPA (20 μM) increased eNOS to 49.I ± 15.2 II/μg protein. The thyroid analog DITPA enhances endothelial nitric oxide and beta-adrenergic-mediated vasorelaxation by increasing nitric oxide in the vasculature.

Original languageEnglish (US)
Pages (from-to)453-459
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume44
Issue number4
DOIs
StatePublished - Oct 2004

Fingerprint

Thyroid Hormones
Vasodilation
Adrenergic Agents
Nitric Oxide
Myocardial Infarction
Acids
Proteins
Blood Pressure
NG-Nitroarginine Methyl Ester
Isoproterenol
Acetylcholine
Sprague Dawley Rats
Arginine
Thyroid Gland
Endothelial Cells
Heart Failure
Clinical Trials

Keywords

  • Beta-adrenergic
  • Heart failure
  • Large artery
  • Nitric oxide
  • Thyroid hormone

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Thyroid hormone analog, DITPA, improves endothelial nitric oxide and beta-adrenergic mediated vasorelaxation after myocardial infarction. / Spooner, Peter H.; Thai, Hoang M.; Goldman, Steven; Gaballa, Mohamed A.

In: Journal of Cardiovascular Pharmacology, Vol. 44, No. 4, 10.2004, p. 453-459.

Research output: Contribution to journalArticle

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abstract = "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 μg/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 mm Hg) but did lower (P < 0.05) LV dP/dt (4633 ± j_ 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 ± 2.8 to 44.5 ± 7.1 integrated intensity units (II)/μg) and in MI rats (5.3 ± 3.4 to 28.3 ± 8.9 II/μg). In endothelial cells, 24 hours' treatment with DITPA (10 μM) increased (P < 0.01) eNOS protein expression from 22.1 ± 4.8 to 52.7 ± 16.8 II/gg protein and DITPA (20 μM) increased eNOS to 49.I ± 15.2 II/μg protein. The thyroid analog DITPA enhances endothelial nitric oxide and beta-adrenergic-mediated vasorelaxation by increasing nitric oxide in the vasculature.",
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N2 - 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 μg/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 mm Hg) but did lower (P < 0.05) LV dP/dt (4633 ± j_ 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 ± 2.8 to 44.5 ± 7.1 integrated intensity units (II)/μg) and in MI rats (5.3 ± 3.4 to 28.3 ± 8.9 II/μg). In endothelial cells, 24 hours' treatment with DITPA (10 μM) increased (P < 0.01) eNOS protein expression from 22.1 ± 4.8 to 52.7 ± 16.8 II/gg protein and DITPA (20 μM) increased eNOS to 49.I ± 15.2 II/μg protein. The thyroid analog DITPA enhances endothelial nitric oxide and beta-adrenergic-mediated vasorelaxation by increasing nitric oxide in the vasculature.

AB - 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 μg/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 mm Hg) but did lower (P < 0.05) LV dP/dt (4633 ± j_ 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 ± 2.8 to 44.5 ± 7.1 integrated intensity units (II)/μg) and in MI rats (5.3 ± 3.4 to 28.3 ± 8.9 II/μg). In endothelial cells, 24 hours' treatment with DITPA (10 μM) increased (P < 0.01) eNOS protein expression from 22.1 ± 4.8 to 52.7 ± 16.8 II/gg protein and DITPA (20 μM) increased eNOS to 49.I ± 15.2 II/μg protein. The thyroid analog DITPA enhances endothelial nitric oxide and beta-adrenergic-mediated vasorelaxation by increasing nitric oxide in the vasculature.

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