Cellular mechanisms of impaired adrenergic responsiveness in neonatal dogs.
Cellular mechanisms of impaired adrenergic responsiveness in neonatal dogs.
复制标题
新生犬肾上腺素能反应受损的细胞机制。
DOI：
10.1172/jci110038
复制
发表时间：
1981
期刊：
影响因子：
--
通讯作者：
Vatner,SF
中科院分区：
文献类型：
--
作者：
Rockson,SG;Homcy,CJ;Quinn,P;Manders,WT;Haber,E;Vatner,SF
在新生儿、6周龄和成年动物中研究了清醒的仪器犬对外源性给予异丙肾上腺素和去甲肾上腺素的心肌反应性。在所有年龄组中观察到左心室压力峰值导数相对于时间的基线值相当。然而，当与成人的反应相比，拟交感神经胺诱导的新生儿左心室dP/dt的增加显着钝化在每个浓度的肾上腺素能激动剂检查，而6周龄的小狗显示中间变力性反应。为了研究这种钝化的新生儿反应的细胞机制，我们将每个年龄组的心肌对儿茶酚胺反应的生理和生物化学测量相关联。与成人心肌膜制剂相比，新生儿心脏膜的特点是在体外的β-肾上腺素能结合位点的密度增加，肾上腺素能激动剂和拮抗剂的亲和力相当，和增强的腺苷酸环化酶激活受体占用耦合。血清中的儿茶酚胺浓度或其他内在蛋白质的膜含量的同时变化未能解释所观察到的新生儿β-肾上腺素能受体密度的增加。这些发现与心脏细胞膜的代偿机制最为一致，即未成熟心肌肾上腺素能反应性的固有抑制似乎诱导受体密度增加和腺苷酸环化酶活化。
The myocardial responsiveness of conscious, instrumental dogs to exogenously administered isoproterenol and norepinephrine was investigated in neonatal, 6-wk-old, and adult animals. Comparable base-line values for peak left ventricular derivative of pressure with respect to time were observed in all age categories. However, when compared with adult responses, the sympathomimetic amine-induced increases in neonatal left ventricular dP/dt were significantly blunted at each concentration of adrenergic agonist examined, whereas the 6-wk-old puppies displayed an intermediate inotropic response. To investigate the cellular mechanisms of this blunted neonatal response, we correlated physiologic and biochemical measurements of the myocardial responses to catecholamines in each age category. When compared with adult myocardial membrane preparations, neonatal cardiac membranes were characterized in vitro by an increased density of beta-adrenergic binding sites, comparable affinity for adrenergic agonists and antagonists, and an enhanced coupling of adenylate cyclase activation to receptor occupancy. Simultaneous changes in either the serum catecholamine concentration or the membrane content of other intrinsic proteins failed to account for the observed neonatal increase in beta-adrenergic receptor density. These findings are most consistent with a compensatory mechanism of the cardiac cell membrane, whereby an inherent depression in the adrenergic responsiveness of the immature myocardium appears to induce the increase in receptor density and activation of adenylate cyclase.