The Effects of Altered Thyroid State Upon Responses Mediated by Atrial Muscarinic Receptors in the Rat

Untreated rats, and rats treated with methimazole (0.05% w/v in drinking water) or thyroxine (1 mg/kg, s.c., three times weekly) for 4-6 weeks to induce hypo- and hyperthyroidism respectively, were used to study the influence of thyroid hormone upon negative chronotropic and inotropic responses mediated by cardiac muscarinic receptors, and upon the affinity of these receptors for atropine. Negative chronotropic effects of methacholine were investigated by establishing partial concentration-response curves for isolated preparations of right atria. Methacholine was least potent in tissues from thyroxine-treated rats. Isolated left atria paced at 3 Hz, and spontaneously beating right atria, were used in studies of the negative inotropic effects of methacholine. This agonist was least potent in atria from the thyroxine-treated rats in which it also produced the smallest maximal responses. The negative inotropic effects of carbachol were examined on left atria paced at 3, 5 and 5.8 Hz to approximate the basal contraction rates of isolated right atria from methimazole-treated, untreated control and thyroxine-treated rats, respectively. At each of these frequencies, carbachol was most potent in atria from methimazole-treated rats, and least potent in atria from thyroxine-treated rats. Maximal responses were smallest in the latter group. pA2 values for atropine with methacholine as the agonist were obtained by the method of Arunlakshana & Schild (1959) for spontaneously beating right atria (negative chronotropic and inotropic effects) and left atria paced at 3 Hz (negative inotropic effects). Slopes of Schild plots did not differ from minus one in tissues from each of the experimental groups; pA2 values were similar, indicating that thyroid status is without effect upon the affinity of this antagonist for muscarinic receptors mediating both negative inotropic and chronotropic effects. 6 The results are discussed in the light of reports that hypothyroidism increases, and hyperthyroidism decreases the numbers of high affinity muscarinic receptor binding sites in the rat myocardium.