Tsujimoto G, Hashimoto K, Hoffman B B
Heart Vessels. 1985 Aug;1(3):152-7. doi: 10.1007/BF02066410.
We have examined the in vivo consequences of prolonged stimulation of the cardiovascular alpha-adrenergic receptor system in a rat model harboring pheochromocytoma. New England Deaconess Hospital rats with transplanted pheochromocytomas developed systolic hypertension and their plasma norepinephrine concentrations were approximately 60-fold greater than controls. Alpha 1-adrenergic receptors were quantitated in hearts from controls and rats with transplanted pheochromocytoma using the alpha 1-receptor selective antagonist [3H]prazosin. Down-regulation of alpha 1-receptors was found in the hearts of pheochromocytoma rats (33.0 vs. 23.0 fmol/mg protein) without any significant change in the affinities of these receptors for the circulating catecholamine, norepinephrine. Furthermore, the responsiveness of the blood vessel to the alpha-adrenergic stimulation was assessed using in vitro contractile experiments. Aortic rings from pheochromocytoma animals showed an eight fold decrease in sensitivity (EC50) and a 74% decrease in maximal contractility (Emax) to norepinephrine as compared with controls. Similarly, mesenteric artery rings prepared from the same animals showed a five fold loss of EC50 but no decrease in Emax to phenylephrine as compared with controls. In addition, serotonin EC50 and Emax of these mesentery preparations remained unaltered. Coupled with our previous findings [9], the present study suggests that rats with pheochromocytoma secreting large amounts of norepinephrine provide a valuable model system for studying in vivo desensitization of the cardiovascular alpha-receptor systems as well as the beta-adrenergic receptor system.
我们已经在携带嗜铬细胞瘤的大鼠模型中研究了心血管α-肾上腺素能受体系统长期刺激的体内后果。移植了嗜铬细胞瘤的新英格兰女执事医院大鼠出现了收缩期高血压，其血浆去甲肾上腺素浓度比对照组高约60倍。使用α1-受体选择性拮抗剂[3H]哌唑嗪对对照组和移植了嗜铬细胞瘤的大鼠心脏中的α1-肾上腺素能受体进行定量。在嗜铬细胞瘤大鼠的心脏中发现α1-受体下调（33.0对23.0 fmol/mg蛋白质），这些受体对循环儿茶酚胺去甲肾上腺素的亲和力没有任何显著变化。此外，使用体外收缩实验评估血管对α-肾上腺素能刺激的反应性。与对照组相比，嗜铬细胞瘤动物的主动脉环对去甲肾上腺素的敏感性（EC50）降低了8倍，最大收缩力（Emax）降低了74%。同样，从相同动物制备的肠系膜动脉环对去氧肾上腺素的EC50降低了5倍，但Emax没有降低。此外，这些肠系膜制剂的5-羟色胺EC50和Emax保持不变。结合我们之前的研究结果[9]，本研究表明，分泌大量去甲肾上腺素的嗜铬细胞瘤大鼠为研究心血管α-受体系统以及β-肾上腺素能受体系统的体内脱敏提供了一个有价值的模型系统。
