Influence of Hyperthyroidism on the Effects of Norepinephrine on Myocardial Adenyl Cyclase Activity and Contractile State

Abstract

Although it has been suggested that hyperthyroidism augments the physiologic effects of catecholamines on the heart, this hypothesis has recently been questioned. Since adenyl cyclase is thought to mediate these physiologic effects, we sought to determine if any biochemical or physiologic evidence of potentiation could be demonstrated by comparing the relative potency of norepinephrine to activate myocardial adenyl cyclase and to augment the intrinsic contractile properties of right ventricular papillary muscles in hearts obtained from euthyroid and hyperthyroid cats. Norepinephrine produced a dose-related (1×10⁻⁸- 5×10⁻⁶m) increase in adenyl cyclase activity in tissue from both euthyroid and hyperthyroid animals; however, no significant differences were observed between the 2 groups at any dose level. In addition, no differences between the groups existed when the net production of cyclic 3′,5′- AMP was examined as a function of the time of incubation. Similarly, no change in sensitivity to norepinephrine was found in the characteristics of papillary muscle isometric tension development. Norepinephrine produced equal doserelated (1 ×10-¹⁰-1×10-⁶m) increases in active tension and rate of tension development in the euthyroid and hyperthyroid animals. Thus, the demonstration that hyperthyroidism does not alter the sensitivity of adenyl cyclase to norepinephrine supports the physiologic observations in the isolated cat papillary muscle suggestting that the hyperdynamic circulatory state of hyperthyroidism is not due to increased cardiac sensitivity to catecholamines. It is of some interest that the threshold concentration of norepinephrine required to activate adenyl cyclase is several orders of magnitude greater than that required to produce an inotropic response; thus, as with most in vitro systems, the exact relationship between enzyme activation and physiologic response is not absolutely certain. (Endocrinology85: 1004, 1969)