Effect of adrenergic agonists on the cyclic AMP level in the liver and heart from normal and hypothyroid rats.

In order to clarify the mechanism of the different sensitivity of the adrenoceptors between normal and hypothyroid rats, cyclic AMP levels in the liver and heart were measured after the administration of phenylephrine, isoproterenol, epinephrine and methoxamine. Cyclic AMP increased in all cases, but the extent of its increment in the heart was much less than that in the liver. Phentolamine and propranolol showed only a partial inhibition of cyclic AMP elevation by the agonists in the liver from normal and hypothyroid rat. On the other hand, propranolol blocked completely the effect of the agonists on the heart from both groups. It was also observed that cyclic AMP increased in adrenalectomized rats after the injection of the adrenergic agonists. The basal activity of protein kinase in hypothyroid status was slightly lower than that in the normal, but this enzyme was stimulated in the presence of cyclic AMP in vitro. These results suggest that the function of beta-adrenoceptor remained normal even in hypothyroidism and responded well to isoproterenol and epinephrine. It is also indicated that the increased sensitivity of alpha-adrenoceptor to phenylephrine in the hy pothyroid atria previously observed is probably in part independent of the mechanism mediated by cyclic AMP.