Ishac E J, Pennefather J N
Br J Pharmacol. 1983 Jun;79(2):451-9. doi: 10.1111/j.1476-5381.1983.tb11018.x.
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.
未治疗的大鼠，以及分别用甲巯咪唑（饮用水中0.05% w/v）或甲状腺素（1 mg/kg，皮下注射，每周三次）处理4 - 6周以分别诱导甲状腺功能减退和甲状腺功能亢进的大鼠，用于研究甲状腺激素对由心脏毒蕈碱受体介导的负性变时性和变力性反应的影响，以及对这些受体与阿托品亲和力的影响。通过建立右心房离体标本的部分浓度 - 反应曲线来研究乙酰甲胆碱的负性变时性作用。乙酰甲胆碱在甲状腺素处理的大鼠组织中效力最低。在研究乙酰甲胆碱的负性变力性作用时，使用以3 Hz起搏的离体左心房和自发搏动的右心房。这种激动剂在甲状腺素处理的大鼠心房中效力最低，在其中它也产生最小的最大反应。在以3、5和5.8 Hz起搏的左心房上检查卡巴胆碱的负性变力性作用，以分别近似甲巯咪唑处理的、未治疗的对照和甲状腺素处理的大鼠离体右心房的基础收缩率。在这些频率中的每一个频率下，卡巴胆碱在甲巯咪唑处理的大鼠心房中效力最高，在甲状腺素处理的大鼠心房中效力最低。后一组的最大反应最小。以乙酰甲胆碱为激动剂时，通过Arunlakshana和Schild（1959年）的方法获得阿托品对自发搏动右心房（负性变时性和变力性作用）和以3 Hz起搏的左心房（负性变力性作用）的pA2值。在每个实验组的组织中，Schild图的斜率与负一没有差异；pA2值相似，表明甲状腺状态对这种拮抗剂与介导负性变力性和变时性作用的毒蕈碱受体的亲和力没有影响。根据甲状腺功能减退会增加、甲状腺功能亢进会减少大鼠心肌中高亲和力毒蕈碱受体结合位点数量的报道，对结果进行了讨论。
