Cardiac effects of 3,5-diiodothyropropionic acid, a thyroid hormone analog with inotropic selectivity

G. D. Pennock, T. E. Raya, J. J. Bahl, Steven Goldman, E. Morkin

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64 Citations (Scopus)

Abstract

Thyroid hormone exerts a strong positive inotropic action on the heart and induces α-myosin heavy chain (MHC) gene expression. 3,5-Diiodothyropropionic acid (DITPA), a carboxylic acid analog with low metabolic activity, was observed to induce α-MHC mRNA in heart cell culture with EC50 ≃ 5 x 10- 7 M. To determine if the compound has positive inotropic actions, the effects of DITPA and L-thyroxine on heart rate, left ventricular pressures, left ventricular dP/dt, myosin isoenzymes and hepatic α-glycerolphosphate dehydrogenase activity were compared in hypothyroid rats. Binding affinities of DITPA and triiodothyronine for bacterially expressed alpha-1 and beta-1 thyroid hormone receptors (TRs) also were determined. Over the dosage range of 150 to 1500 μg/100 g, DITPA produced increases in left ventricular dP/dt comparable to those obtained with L-thyroxine at dosages of 1.5 to 15 μg/100 g, but with significantly less tachycardia. The increase in α-MHC mRNA was about the same with both compounds whereas α-MHC protein content and GPDH activity increased less with DITPA. These differences could not be explained by preferential binding of DITPA to TR subtypes. Because heart rate is a major determinant of myocardial oxygen consumption, DITPA is able to achieve increased cardiac performance at lower myocardial oxygen costs.

Original languageEnglish (US)
Pages (from-to)163-169
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume263
Issue number1
StatePublished - 1992

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Thyroid Hormones
Myosin Heavy Chains
Thyroxine
Thyroid Hormone Receptors beta
Heart Rate
Glycerolphosphate Dehydrogenase
Thyroid Hormone Receptors
Messenger RNA
Triiodothyronine
Ventricular Pressure
Myosins
Carboxylic Acids
3,5-diiodothyropropionic acid
Tachycardia
Oxygen Consumption
Isoenzymes
Cell Culture Techniques
Oxygen
Gene Expression
Costs and Cost Analysis

ASJC Scopus subject areas

  • Pharmacology

Cite this

Cardiac effects of 3,5-diiodothyropropionic acid, a thyroid hormone analog with inotropic selectivity. / Pennock, G. D.; Raya, T. E.; Bahl, J. J.; Goldman, Steven; Morkin, E.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 263, No. 1, 1992, p. 163-169.

Research output: Contribution to journalArticle

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