Brown L, Wyse B, Sernia C
Department of Physiology and Pharmacology, University of Queensland, Australia.
Biochem Pharmacol. 1993 Jun 9;45(11):2223-9. doi: 10.1016/0006-2952(93)90193-z.
This study has measured cardiovascular parameters, pharmacological responses to alpha- and beta-adrenoceptor agonists, and cardiac beta-adrenoceptor characteristics in growth hormone (GH)-deficient (dwarf) Lewis rats, normal Lewis rats and dwarf rats treated with GH (2 mg/kg/day for 28 days). Dwarf rats showed a decrease mean blood pressure and heart rate but an increased ventricular weight relative to body weight when compared with age-matched normal Lewis rats. Positive chronotropic responses in vivo to the non-selective beta-adrenoceptor agonist, isoprenaline, were unchanged in dwarf rats. The selective beta 1-adrenoceptor agonist, noradrenaline, was less potent in isolated right atria from dwarf rats although maximal responses were unchanged. Basal force of contraction was greater in isolated cardiac muscles from dwarf rats than from normal rats. Maximal positive inotropic responses to both calcium chloride and noradrenaline were reduced in left atria but increased in left ventricular papillary muscles from dwarf rats. Responses to the alpha 1-adrenoceptor agonist, phenylephrine, were markedly increased in isolated cardiac tissues from dwarf rats. Maximal contractile responses of isolated thoracic aortic rings from dwarf rats to KCl (100 mM) and the alpha-adrenoceptor agonist, noradrenaline, were markedly reduced compared to responses in normal rats. Left ventricular beta-adrenoceptor density measured by 125I-cyanopindolol binding was significantly increased in dwarf rats. Administration of GH (2 mg/kg/day for 28 days) reversed the altered responses in dwarf rats. We conclude that GH: (a) is required for the development of normal contractile capability of cardiac and vascular tissues; (b) regulates both beta-adrenoceptors and alpha- and beta-adrenoceptor-mediated responses; (c) differentially regulates atrial and ventricular responsiveness.
本研究测量了生长激素（GH）缺乏（侏儒）的Lewis大鼠、正常Lewis大鼠以及接受GH治疗（2毫克/千克/天，持续28天）的侏儒大鼠的心血管参数、对α和β肾上腺素能受体激动剂的药理反应以及心脏β肾上腺素能受体特征。与年龄匹配的正常Lewis大鼠相比，侏儒大鼠的平均血压和心率降低，但心室重量相对于体重增加。侏儒大鼠对非选择性β肾上腺素能受体激动剂异丙肾上腺素的体内变时反应未发生改变。选择性β1肾上腺素能受体激动剂去甲肾上腺素对侏儒大鼠离体右心房的作用较弱，尽管最大反应未变。侏儒大鼠离体心肌的基础收缩力比正常大鼠更大。侏儒大鼠左心房对氯化钙和去甲肾上腺素的最大正性变力反应降低，但左心室乳头肌的反应增强。侏儒大鼠离体心脏组织对α1肾上腺素能受体激动剂去氧肾上腺素的反应明显增强。与正常大鼠相比，侏儒大鼠离体胸主动脉环对氯化钾（100毫摩尔）和α肾上腺素能受体激动剂去甲肾上腺素的最大收缩反应明显降低。通过125I-氰吲哚洛尔结合测定的左心室β肾上腺素能受体密度在侏儒大鼠中显著增加。给予GH（2毫克/千克/天，持续28天）可逆转侏儒大鼠的反应改变。我们得出结论：（a）心脏和血管组织正常收缩能力的发展需要GH；（b）GH调节β肾上腺素能受体以及α和β肾上腺素能受体介导的反应；（c）GH对心房和心室反应性的调节存在差异。
