Effect of Changes in Thyroid State on Atrial α- and β-Adrenoceptors, Adenylate Cyclase Activity, and Catecholamine Levels in the Rat

Abstract

The effects of altered thyroid state on catecholamine levels, adrenoceptor agonist potencies, and adenylate cyclase activity have been investigated using rat atria in an attempt to determine any correlation between thyroid-induced changes in these parameters. Hypothyroidism was associated with decreased growth rate, heart rate and weight, and hypertrophy of the thyroid gland; norepinephrine concentration in combined atria was also reduced. Hyperthyroid rats displayed tachycardia and marked cardiac hypertrophy, but unchanged atrial norepinephrine concentration. Measurements of inotropic potencies of phenylephrine, norepinephrine, and isoproterenol using paced left atria from hypothyroid rats indicated a possible increase in number, but not in affinity, of alpha-adrenoceptors relative to beta-adrenoceptors. The reverse was observed in hyperthyroidism. However, similar changes were not obtained when chronotropic responses to the three amines were examined using spontaneously beating right atrial preparations. Our results suggest that only in the hypothyroid state do alpha-adrenoceptors contribute significantly to the positive inotropic response to catecholamines. Adenylate cyclase activation by isoproterenol and fluoride ion was reduced in atrial membrane preparations from hypothyroid rats. Taken together, these results suggest that thyroid state modifies both pre- and post-junctional adrenergic mechanisms in rat atria.