Long-term physiological T3 supplementation in hypertensive heart disease in rats

Am J Physiol Heart Circ Physiol. 2015 Sep 15;309(6):H1059-65. doi: 10.1152/ajpheart.00431.2015. Epub 2015 Aug 7.

Abstract

Animal studies suggest that hypertension leads to cardiac tissue hypothyroidism, a condition that can by itself lead to heart failure. We have previously shown that short-term thyroid hormone treatment in Spontaneously Hypertensive Heart Failure (SHHF) rats near heart failure is beneficial. This study tested the hypothesis that therapeutic, long-term T3 treatment in SHHF rats can prevent or attenuate cardiac dysfunction. Female SHHF rats were treated orally with a physiological T3 dose (0.04 μg/ml) from 12 to 24 mo of age. Age-matched female SHHF and Wistar-Kyoto rats served as hypertensive and normotensive controls, respectively. SHHF rats had reduced serum free thyroid hormone levels and cardiac tissue T3 levels, LV dysfunction, and elevated LV collagen content compared with normotensive controls. Restoration of serum and cardiac tissue thyroid hormone levels in T3-treated rats was associated with no change in heart rate, but strong trends for improvement in LV systolic function and collagen levels. For instance, end-systolic diameter, fractional shortening, systolic wall stress, and LV collagen levels were no longer significantly different from controls. In conclusion, longstanding hypertension in rats led to chronic low serum and cardiac tissue thyroid hormone levels. Long-term treatment with low-dose T3 was safe. While cardiac dysfunction could not be completely prevented in the absence of antihypertensive treatment, T3 may offer additional benefits as an adjunct therapy with possible improvement in diastolic function.

Keywords: fibrosis; heart failure; hypertension; left ventricle; thyroid hormone.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Collagen / drug effects*
  • Collagen / metabolism
  • Female
  • Heart / drug effects*
  • Heart Failure / etiology*
  • Heart Failure / metabolism
  • Heart Ventricles / drug effects*
  • Heart Ventricles / metabolism
  • Hypertension / complications*
  • Hypertension / metabolism
  • Hypothyroidism / etiology*
  • Hypothyroidism / metabolism
  • Myosins / drug effects
  • Myosins / metabolism
  • Random Allocation
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Thyroxine / metabolism
  • Triiodothyronine / pharmacology*
  • Ventricular Dysfunction, Left / etiology*
  • Ventricular Dysfunction, Left / metabolism
  • Ventricular Function, Left / drug effects*

Substances

  • Triiodothyronine
  • Collagen
  • Myosins
  • Thyroxine