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

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

Research output: Contribution to journalArticle

66 Scopus citations

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 - Jan 1 1992

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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