Brown L, Nankervis R, Kerr D, Sernia C
Department of Physiology and Pharmacology, University of Queensland, Australia.
Biochem Pharmacol. 1994 Jan 20;47(2):281-8. doi: 10.1016/0006-2952(94)90018-3.
This study has investigated adrenoceptor-mediated responses and beta-adrenoceptors in neonatal-onset hypothyroidism in rats. Four groups of adult rats were studied: controls, neonatal-onset uncorrected hypothyroidism (continuous oral methimazole treatment) and after chronic triiodothyronine (T3) replacement of these rats at either 25 or 100 micrograms/kg/day for 8 weeks beginning at 12 weeks of age. Hypothyroid rats were 61% smaller with an 18% decrease in heart rate; food and water intake were reduced to 43% and 52%, respectively; O2 consumption was reduced to 20% and rectal temperature was 2.9 degrees lower. T3 administration increased body weight to 60-62% of controls; metabolic changes were reversed; but tachycardia and cardiac hypertrophy (60-120% increases) resulted. The positive inotropic responses to the selective alpha 1-adrenoceptor agonist, phenylephrine, in left ventricular papillary muscles were abolished; the beta 1-adrenoceptor agonist, noradrenaline, was significantly less potent as an inotropic compound in isolated cardiac tissues from hypothyroid rats. The potency of phenylephrine to contract thoracic aortic rings was reduced in hypothyroid rats. These changes in alpha- and beta-adrenoceptor mediated responses were reversed by T3 administration. Both beta 1- and beta 2-adrenoceptor densities were increased in the hypothyroid left ventricle; T3 administration further increased beta 1-adrenoceptor density. We conclude that neonatal hypothyroidism produces pronounced physiological responses, changes in adrenoceptor-mediated responses and an increased ventricular beta 1-adrenoceptor density. T3 replacement reversed the changes in cardiac responses and metabolic parameters, except body weight, but produced cardiac symptoms of hyperthyroidism (tachycardia, hypertrophy as well as an increased beta 1-adrenoceptor density).
本研究调查了新生期甲状腺功能减退大鼠中肾上腺素能受体介导的反应及β-肾上腺素能受体。研究了四组成年大鼠：对照组、新生期未纠正的甲状腺功能减退组（持续口服甲巯咪唑治疗），以及在这些大鼠12周龄时开始以25或100微克/千克/天的剂量进行慢性三碘甲状腺原氨酸（T3）替代治疗8周后的组。甲状腺功能减退的大鼠体重小61%，心率降低18%；食物和水的摄入量分别降至43%和52%；耗氧量降至20%，直肠温度低2.9摄氏度。给予T3后体重增加至对照组的60 - 62%；代谢变化得到逆转；但出现了心动过速和心脏肥大（增加60 - 120%）。对选择性α1-肾上腺素能受体激动剂去氧肾上腺素的左心室乳头肌正性肌力反应消失；β1-肾上腺素能受体激动剂去甲肾上腺素作为一种变力化合物在甲状腺功能减退大鼠的离体心脏组织中的效力显著降低。去氧肾上腺素收缩胸主动脉环的效力在甲状腺功能减退大鼠中降低。这些α-和β-肾上腺素能受体介导反应的变化通过给予T3得以逆转。甲状腺功能减退的左心室中β1-和β2-肾上腺素能受体密度均增加；给予T3进一步增加了β1-肾上腺素能受体密度。我们得出结论，新生期甲状腺功能减退会产生明显的生理反应、肾上腺素能受体介导反应的变化以及心室β1-肾上腺素能受体密度增加。T3替代逆转了心脏反应和代谢参数的变化，但体重未恢复，且产生了甲状腺功能亢进的心脏症状（心动过速、肥大以及β1-肾上腺素能受体密度增加）。
