Department of Pharmacology, Faculty of Pharmacy, Ankara University, 06100 Tandogan, Ankara, Turkey.
Mol Cell Biochem. 2010 Feb;335(1-2):59-66. doi: 10.1007/s11010-009-0241-z. Epub 2009 Sep 1.
Thyroid hormone deficiency has been reported to decrease expression and function of both beta(1)- and beta(2)-adrenoceptor in different tissues including heart. The purpose of this study was to examine the possible contribution of beta(3)-adrenoceptors to cardiac dysfunction in hypothyroidism. In addition, effect of this pathology on beta(1)- and beta(2)-adrenoceptor was investigated. Hypothyroidism was induced by adding methimazole (300 mg/l) to drinking water of rats for 8 weeks. Cardiac hemodynamic parameters were measured in anesthetised rats in vivo. Responses to beta-adrenoceptor agonists were examined in rat papillary muscle in vitro. We also studied the effect of hypotyroidism on mRNA expression of beta-adrenoceptors, Gialpha, GRK, and eNOS in rat heart. All of the hemodynamic parameters (systolic, diastolic and mean arterial pressure, left ventricular pressure, heart rate, +dp/dt, and -dp/dt) were significantly reduced by the methimazole treatment. The negative inotropic effect elicited by BRL 37344 (a beta(3)-adrenoceptor preferential agonist) and positive inotropic effects produced by isoprenaline and noradrenaline, respectively, were significantly decreased in papillary muscle of hypothyroid rats as compared to those of controls. On the other hand, hypothyroidism resulted in increased cardiac beta(2)- and beta(3)-adrenoceptor, Gialpha(2), Gialpha(3), GRK3, and eNOS mRNA expressions. However, beta(1)-adrenoceptor and GRK2 mRNA expressions were not changed significantly in this pathology. These results show that mRNA expression of beta(3)-adrenoceptors as well as the signalling pathway components mediated through beta(3)-adrenoceptors are significantly increased in hypothyroid rat heart. Since we could not correlate these alternates with the decreased negative inotropic response mediated by this receptor subtype, it is not clear whether these changes are important for hypothyroid induced reduction in cardiac function.
甲状腺激素缺乏已被报道可降低β（1）-和β（2）-肾上腺素能受体在包括心脏在内的不同组织中的表达和功能。本研究的目的是研究β（3）-肾上腺素能受体在甲状腺功能减退症心脏功能障碍中的可能作用。此外，还研究了这种病理学对β（1）-和β（2）-肾上腺素能受体的影响。通过在大鼠饮用水中添加甲巯咪唑（300mg/L）诱导甲状腺功能减退症 8 周。在麻醉大鼠体内测量心脏血流动力学参数。在大鼠乳头肌体外研究β-肾上腺素受体激动剂的反应。我们还研究了甲状腺功能减退症对大鼠心脏β-肾上腺素能受体、Gialpha、GRK 和 eNOS mRNA 表达的影响。所有血流动力学参数（收缩压、舒张压和平均动脉压、左心室压、心率、+dp/dt 和-dp/dt）均因甲巯咪唑治疗而显著降低。BRL 37344（β（3）-肾上腺素能受体选择性激动剂）引起的负性肌力作用和异丙肾上腺素和去甲肾上腺素分别产生的正性肌力作用在甲状腺功能减退症大鼠的乳头肌中均明显低于对照组。另一方面，甲状腺功能减退症导致心脏β（2）-和β（3）-肾上腺素能受体、Gialpha（2）、Gialpha（3）、GRK3 和 eNOS mRNA 表达增加。然而，在这种病理中，β（1）-肾上腺素能受体和 GRK2 mRNA 表达没有明显变化。这些结果表明，β（3）-肾上腺素能受体的 mRNA 表达以及通过β（3）-肾上腺素能受体介导的信号通路组成部分在甲状腺功能减退症大鼠心脏中显著增加。由于我们无法将这些改变与该受体亚型介导的负性肌力反应的降低相关联，因此尚不清楚这些改变是否对甲状腺功能减退症引起的心脏功能降低很重要。
