Effects of thyroid deficiency and sympathectomy on cardiac enzymes

Abstract

The effects of thyroid deficiency (Td) and of chemical sympathectomy (Sx) were studied on marker enzymes of energy metabolism in cardiac muscle of neonatal and of adult rats. Td prevented the normal development of neonatal body weight, relative heart mass, and cardiac levels of cytochrome c (-22%), citrate synthase (-27%), phosphofructokinase (-20%) and Mg2+- and Ca2+-ATPase activity of purified myofibrils (-33%, -44%). Exogenous thyroxin replacement restored those parameters studied to normal with the exception that it persistently elevated citrate synthase activity significantly above normal control levels. Responses similar to those of Td neonates occurred when adult rats were similarly treated. Sx produced no consistent effects on respiratory and glycogenolytic marker enzymes, but caused a 20% reduction in Ca2+-ATPase activity of both neonatal and adult cardiac myofibrils. These findings suggest that cardiac muscle cells require thyroxin for normal growth and enzyme development. Also, Sx may impair cardiac functional capacity by altering Ca2+ activity of actomyosin ATPase.

Effect of hypothyroidism on the expression of cytochrome c and cytochrome c oxidase in heart and muscle during development

“…Although thyroid hormone is known to affect the extent of the increase in mitochondrial enzymes during development [9,10], our data also suggest that the magnitude of the hormone effect depends on the muscle type. In heart, hypothyroidism attenuated the accumulation of CYTOX throughout the developmental period studied, including the fetal stage.…”

“…In addition, increases in intrinsic heart rate and the capacity for pressure development [7,8] imply that cardiac energy requirements are also increased during the early post-natal period. Although some data exist in skeletal muscle and heart during the later stages of development with respect to increases in mitochondrial enzymes [9,10] and cytochromes [ 11 ], studies encompassing the early post-natal time points during which profound changes in mitochondrial composition occur are lacking.…”

“…For example, the hypothyroid state results in the suppression of mitochondrial enzyme activities during development [9,10]. Thyroid hormone has also been found to have a variable effect on the expression of nuclear genes encoding mitochondrial proteins in adult liver [12,13], indicating genespecific regulation by the hormone.…”

Influence of thyroid hormone on the tissue-specific expression of cytochrome c oxidase isoforms during cardiac development

“…Thyroid hormone is known to stimulate mitochondrial biogenesis in most tissues [28][29][30], and an induced thyroid deficiency produces reductions in COX activities and mRNA levels in liver [29,31], cardiac [10,32,33] and skeletal muscle [10,29,34]. Furthermore thyroid hormone has previously been shown to regulate the expression of contractile proteins in muscle, causing a developmental switch of myosin heavy chain (MHC) isoforms in cardiac and skeletal muscle [35,36].…”

The hyperthyroid heart. An analysis of systolic and diastolic properties in single rat ventricular myocytes.

“…[1][2][3][4][5][6][7][8] The rat model has been fairly well characterized in this regard. [9][10][11][12] Daily intramuscular injection of adult (500-600 g) rats with thyroxine (6.4 mg/kg initial body wt/day for 7 days), which produces a marked hyperthyroid state, increases serum thyroxine levels 10-fold, decreases body weight 10%, increases left ventricular weight 35%, and shifts the myosin isoenzyme distribution to predominately Vl.9 Electrophysiological study of isolated muscle indicates that the hyperthyroid state as produced above prolongs the action potential duration by approximately 50%.…”