Manger W M, Hulse M C, Forsyth M S, Chute R N, Brown C E, Webb K, Sussman R, Warren S
Hypertension. 1982 May-Jun;4(3 Pt 2):200-7.
The New England Deaconess Hospital (NEDH) rat provides a valuable model with which to study pheochromocytoma (P); 59% of male rats 700 to 900 days old and 81% of those 900 days or older developed spontaneous P. One transplantable P (P259), when implanted into other NEDH rats, markedly increased plasma norepinephrine and dopamine as well as blood pressure, and usually caused death within 4 weeks. Even without P, about 83% of NEDH rats became hypertensive by 131/2 weeks of age and remained moderately hypertensive until 2 years of age when some animals developed spontaneous P and hypertension became severe. Whether a common mechanism is responsible for early appearance of hypertension and later development of P remains to be determined. Hypophysectomized NEDH rats remained normotensive or slightly hypotensive despite marked elevations of plasma norepinephrine and dopamine caused by P259 implantation; furthermore, survival was prolonged to 3 months. Catecholamine concentrations in plasma and RBC were usually quite similar, indicating that red blood cells play a significant role in inactivating circulating catecholamines. Unlike the normal adrenal, P259 in NEDH rats contains mainly norepinephrine and dopamine with little epinephrine; it appears that P259 is deficient in the enzyme phenylethanolamine-N-methyltransferase (PNMT), which converts norepinephrine to epinephrine. Why hypophysectomy prevents hypertension and prolongs life in rats with P259 implants is unclear; adrenal cortical and thyroid deficiency may play a role. Preliminary observations indicate that hypophysectomy can prevent spontaneous development of P in NEDH rats.
新英格兰女执事医院（NEDH）大鼠为研究嗜铬细胞瘤（P）提供了一个有价值的模型；700至900日龄的雄性大鼠中有59%以及900日龄及以上的大鼠中有81%会发生自发性嗜铬细胞瘤。一种可移植的嗜铬细胞瘤（P259）植入其他NEDH大鼠体内时，会显著升高血浆去甲肾上腺素和多巴胺水平以及血压，通常在4周内导致死亡。即使没有嗜铬细胞瘤，约83%的NEDH大鼠在13.5周龄时会出现高血压，并在2岁时一直保持中度高血压，此时一些动物会发生自发性嗜铬细胞瘤，高血压会变得严重。高血压的早期出现和后期嗜铬细胞瘤的发生是否由共同机制引起仍有待确定。垂体切除的NEDH大鼠尽管因植入P259而导致血浆去甲肾上腺素和多巴胺显著升高，但仍保持血压正常或轻度低血压；此外，生存期延长至3个月。血浆和红细胞中的儿茶酚胺浓度通常非常相似，表明红细胞在使循环中的儿茶酚胺失活方面发挥着重要作用。与正常肾上腺不同，NEDH大鼠中的P259主要含有去甲肾上腺素和多巴胺，肾上腺素含量很少；看来P259缺乏将去甲肾上腺素转化为肾上腺素的苯乙醇胺-N-甲基转移酶（PNMT）。垂体切除为何能预防植入P259的大鼠发生高血压并延长其寿命尚不清楚；肾上腺皮质和甲状腺功能减退可能起了作用。初步观察表明，垂体切除可预防NEDH大鼠自发性嗜铬细胞瘤的发生。
