Hypothyroid Rat Heart Research Articles

EFFECT OF HYPOTHYROID STATUS ON ADENOSINE 3′,5′-MONO-PHOSPHATE-DEPENDENT PROTEIN KINASE OF SKELETAL, HEART AND DIAPHRAGM MUSCLE OF RATS

AbstractProperties of cyclic AMP-dependent protein kinases from skeletal, heart and diaphragm muscles of hypothyroid rats were compared. Increased enzyme activity was observed in skeletal muscle from hypothyroid rats after DEAE-cellulose chromatography. Changes in isozyme distribution were also shown in the hypothyroid status. The elution profile on DEAE-cellulose suggested a possible translocation of the enzyme from the particulate to the soluble fraction in the heart of hypothyroid rats. The turnover rate of the enzyme protein decreased in the skeletal muscle of hypothyroid rats, but the other two organs showed no change even in the hypothyroid status. The activity of heat-stable protein kinase inhibitor increased in the skeletal and the diaphragm muscles in hypothyroid rats, whereas the activity in the heart decreased in the hypothyroid status. These data suggested the possibility that changes in enzyme properties, modification of isozyme distribution, and changes in modulator activity might account for the modulation of muscle function in hypothyroid rats.

Cardiac electrolytes and water in thyroparathyroidectomized rat

The effect of thyroparathyroidectomy (TPTX) on myocardial extracellular space (ECS), water and electrolytes was studied in young, female, Sprague-Dawley rats. Eight weeks after TPTX the ventricular ECS, measured in vivo with [ 35S]sulfate, was found to be 0.219 ± 0.004 (g H 2O/g tissue as compared to 0.177 ± 0.006 in euthyroid control rats. Measurement of ECS in the same ventricular tissue of TPTX rat by a morphometric procedure confirmed the increase: 0.209 ± 0.004 (cm 3/cm 3). This increase in ECS was only relative to the size of the cellular compartment, for the absolute volume of the ECS in the ventricular myocardium fell. Thus, the relative expansion of the ECS at the expense of the cellular compartment appears to be due to a greater sensitivity of the parenchyma to the inhibitory effects of hypothyroidism on growth. This finding is compatible with a decrease in cellular size of the hearts of hypothyroid rats; a compartmental shift in water from the cellular to the extracellular compartment need not be postulated. Most or all of the enlargement of ECS is due to an expansion of the interstitial compartment. No changes in tissue water content were detected. Plasma concentrations of potassium, calcium and magnesium declined, whereas the concentrations of sodium and chloride remained constant. Depending on whether the electrolytes are predominantly intracellular or extracellular, tissue electrolyte contents showed alterations appropriate to the relative changes in compartmental volumes. Assuming homogeneous distributions of the electrolytes throughout the ECS, the calculated cellular concentrations slightly increased for sodium and potassium, decreased for magnesium, and remained unchanged for calcium and chloride.

Increased heart adenylcyclase activity in the hypothyroid rat

Adenylcyclase activity was measured in heart homogenates and membrane fractions from normal and hypothyroid rats. Much more activity was found in hypothyroid animals than in normal controls. Thyroxine in vitro has no action on the enzyme activity from normal animals, and a slight depressing action on the enzyme from hypothyroid animals. Oral thyroxine treatment of thyroid deprived rats tends to lower the heart adenylcyclase activity towards normal values. Adenylcyclase increase seems to be due to activation rather than to enzyme synthesis. This activation could not be ascribed, however, to TSH increase, because TSH in vitro does not influence the enzyme from normal rat heart. Similarly, the activation could not be ascribed to myocardial catecholamine increase, because the β-blocking agent propranolol does not lower the enzyme activity from hypothyroid rat heart, and also because DOPAmine does not increase the adenylcyclase activity from normal rat heart. It is concluded that activation of adenylcyclase cannot account for the cardiac effects of thyroid hormones.

Oxygen consumption of the auricles, right and left ventricles of the normal, hypothyroid rat heart.

A study of the oxygen consumption of the atrium, right and left ventricles from rat heart has been reported. The response of these heart regions to the in vitro and in vivo addition of thyroxine has been reported. Results obtained were: a) The oxygen consumption of the left ventricle from normal animals was found to be about 25% greater than that of the right ventricle and atrium. b) In animals whose thyroid activity was depressed the oxygen consumption of the atrium and the right and left ventricles was proportionately decreased about 25%. c) Animals whose thyroid activity was increased were found to have an increased oxygen consumption in all areas of the heart, however, not proportionately. d) The in vitro addition of thyroxine to the three heart areas from animals with decreased thyroid activity and normal animals caused an increase in oxygen consumption, whereas it did not appreciably affect the oxygen consumption of the heart areas from animals with increased thyroid activity.