Disorders of Catecholamine Metabolism in Hyperthyroidism:with Special References to Cardiovascular Responses to Catecholamines

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Previous investigation at our laboratory revealed that cardiovascular responses to administered isoproterenol and propranolol were markedly more intense in hyperthyroid patients than those in normal subjects. These results suggested that responsiveness of the β -adrenergic receptor in the cardiovascular system would be augumented in these patients. In order to investigate the mechanism underlying hyper-function of the β -adrenergic receptor in hyperthyroidism, any possible influence of ferrous ion on vasoconstrictive response to catecholamines in hyperthyroid animals was studied. Rabbits and rats which had been found to be hyperthyroid animals were given thyradin for 14 to 21 days and elevation of protein-bound iodine levels were observed. Perfusion of rabbit ear vessels and rat hind limbs was performed by the method of constant perfusion pressure (Krawkow-Pissemski) and the constant perfusion flow (Perpex Pump), respectively. Response of the vessels to infusion of catecholamines were observed under various conditions. The results were as follows: I) Experiments on rabbit ear vessels: 1) Vasoconstrictive response to noradrenaline (0.05 μ g /0.5 ml) and adrenaline (0.05 μg/0.5 ml) in the hyperthyroid animals was significantly lower than those in normal animals. 2) In normal rabbits, perfusion of 1,500 ml of 1 mM α, -dipyridyl produced a marked reduction of the vasoconstrictive responses to catecholamines. After this procedure, ferrous ion was administrated. The vasoconstrictive response was increased by a small dose (1 mM FeSO4, 0.1 ml) and decreased by a large dose (0.1 ml of 1/100 M) of ferrous ion. In the hyperthyroid rabbit ear, the vasoconstrictive responses to catecholamines were increased by perfusion of α, -dipyridyl. Pretreatment by both a small and a large doses of ferrous ion resulted in decrease of these responses. II) Experiments on rat hind limbs: 1) Basal perfusion pressure in the hyperthyroid rat (16.4 ± 2.3 mmHg) was same as that in normal rat (16.3± 1.5 mmHg) under these experimental conditions (1.25 ml/ min constant perfused). Rise in pressure following administration of noradrenaline (0.5 μ g/0.1 ml) and adrenaline (0.5 μ g/0.1 ml) have tendency to be lowered in the hyperthyroid rat than in normal rats, respectively. 2) After perfusion of 37.5ml of 2 mM α, -dipyridyl, pressor responses to noradre-naline and adrenaline were decreased both in the hyperthyroid and normal rats. Thereafter, administration of a small dose of ferrous ion (0.1 ml of 1 mM FeSO4/) resulted in augmentation of the pressor response to catecholamines in normal rats. However, this augmentation was not observed in the hyperthyroid rats. Followingadministration of a large dose of ferrous ion (0.1 ml of 1/100 M FeSO4), the response to noradrenaline and adrenaline was decreased in normal rats, while it was increased in the hyperthyroid rats. The effects of a small dose and a large one of ferrous ion were compared between the normal and hyperthyroid rats, and a statistically significant difference was observed (noradrenaline: p< 0.02, adrenaline: p< 0.05). These findings suggest that the cardiovascular abnormalities observed in hyperthyroidism may be related, in part at least, to disorder of ferrous ion metabolism.
Japan Society of Clinical Chemistryの論文

Disorders of Catecholamine Metabolism in Hyperthyroidism:with Special References to Cardiovascular Responses to Catecholamines

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