Physiological Regulation of Cardiac Alpha Adrenergic Receptors

在目前的工作中，我们首次利用α-1选择性拮抗剂[~3H]哌唑嗪作为放射性配基，表征了大鼠心肌膜制剂中的α-1肾上腺素能受体。然后，研究了这些受体在衰老、甲状腺激素和嗜铬细胞瘤等多种生理和病理生理情况下的体内调节。比较年轻(2月龄)和老年(12月龄)大鼠，我们发现心肌α-1受体的数量随着年龄的增长而减少。用甲状腺激素治疗后，发现老年大鼠的心脏α-1受体密度进一步降低，提示甲状腺激素和衰老对心脏α-1受体有不同的影响，这两个生理变量是独立相关的。接下来，我们研究了长时间刺激心脏α-受体对嗜铬细胞瘤大鼠模型的影响。在嗜铬细胞瘤大鼠的心脏中发现α-1受体的显著下调。这些受体与循环中的儿茶酚胺的亲和力没有任何显著变化。综上所述，这些研究清楚地表明，心脏α肾上腺素能受体可以像心脏β受体一样在体内受到动态调节。

In the present work, we first characterized alpha-1 adrenergic receptors in rat cardiac membrane preparation, utilizing alpha-1 selective antagonist [^3H]prazosin as a radioligand. Then, the in vivo regulation of these receptors in a variety of physiologic and pathophysiological situations including aging,thyroid hormone and pheochromocytoma was studied Comparing young (2 month-old) and older (12 month-old)rats, we found that there was an age-related decreae in the number of myocardial alpha-1 receptors. With thyroid hormone treatment, the density of ventricular alpha-1 receptors was found to be further reduced even in the older rats, suggesting that thyroid hormone and aging have different influences on the cardiac alpha-1 receptors and these two physiological variables are independently interrelated Next, we have examined the consequences of prolonged stimulation of the cardiac alpha receptors in a rat model harboring pheochromocytoma. A marked down-regulation of alpha-1 receptors was found in the hearts of pheochromocytoma rats.without any significant change in the affinities of these receptors for the circulating catecholamine. In summary,these studies cleary demonstrate that the cardiac alpha adrenergic receptors can be dynamically regulated in vivo like cardiac beta receptors.