Cardiac responsiveness to alpha and beta adrenergic amines: effects of carbachol and hypothyroidism

Previous reports of cardiac beta to alpha adrenoceptor interconversion secondary to hypothyroidism left open the alternative possibility of a functional influence by hypothyroidism on the inotropic and chronotropic effects of adrenergic amines through a different mechanism. To test this possibility, the effects of hypothyroidism (thyroidectomy) were compared with those of acute carbachol pretreatment on the responses of isolated rat atria to the selective beta and alpha adrenoceptor agonists isoproterenol and methoxamine. Both hypothyroidism and acute carbachol pretreatment (3 X 10(-7) -10(-6) M): 1) reduced basal right atrial rates and left atrial tensions; 2) caused an apparent decrease in the inotropic and chronotropic potencies of isoproterenol; 3) reduced the degree of antagonism by propranolol of the responses to isoproterenol; 4) increased the maximum inotropic response of left atria to methoxamine; and 5) converted a lack of response to a positive chronotropic response of right atria to methoxamine. Equivalent reductions of basal rates by hypothermia, or of basal tensions by lowered calcium ion concentrations, did not affect the responses to isoproterenol or methoxamine. The results suggest that both carbachol pretreatment and hypothyroidism functionally antagonize the responses to isoproterenol and enhance the responses to methoxamine by means other than adrenoceptor interconversion.