Thyroid Function and the Cardiac Disposition of Catecholamines

Abstract

Hyperthyroid rats show an elevated and prolonged hemodynamic response to injected epinephrine; hypothyroid rats have lower base-line blood pressures than control animals, but show a normal response to the catecholamine. Hyperthyroid rats shunt a larger fraction of the cardiac output to their enlarged hearts, thus delivering a greater proportion of a dose of H³-epinephrine to this organ. Each gram of hyperthyroid heart receives the same fraction of circulating H³-epinephrine as an equal weight of normal heart, but its capacity to inactivate the H³-epinephrine by binding is diminished. The consequent maintenance of elevated levels of free epinephrine may be a major factor in the development of the altered hemodynamic response of the hyperthyroid animal to epinephrine. A single large dose of thyroxine has no effect on the uptake, binding or release of H³- epinephrine by the heart, or the hypertensive response induced by a given dose of the neurohumor. Hypothyroid hearts receive and bind as much circulating epinephrine as normal hearts, in spite of their decreased weight. One hour after H³-epinephrine administration they contain greater amounts of the H³-metabolites, while hyperthyroid hearts contain smaller quantities. This difference is probably related to washout by the circulating blood. Although hyperthyroidism increases hepatic monoamine oxidase activity in the female, and hypothyroidism decreases it in the male, hyperthyroidism is associated with a decrease and hypothyroidism with an increase in deaminated metabolites of H³-epinephrine in the heart. Neither cardiac nor hepatic catechol-Omethyl transferase activity is altered by doses of thyroxine which produce hyperresponsiveness to epinephrine. It is concluded that at least a part of the mechanism of the increased cardiovascular sensitivity to epinephrine found in hyperthyroidism is not due to changes in the activities of the enzymes which metabolize epinephrine, but is related to a decreased ability of each unit weight of heart to inactivate this catecholamine by binding. More “free” epinephrine is available in the heart to act on its physiologic receptors.