The effect of a calcium antagonist and ATP on blood pressure in a rat model of pheochromocytoma

首先，我们尝试建立大鼠嗜铬细胞瘤模型。10 ~ 12周龄新英格兰执事医院（NEDH）大鼠在肩胛间区皮下接种0.5 × 10^6个嗜铬细胞瘤细胞（PC-12）。接种后，肿瘤在3-4周后首次可触及。接种后5-6周首次发现收缩压和心率升高。接种后4周尿中儿茶酚胺排泄量增加。特别是，与对照组相比，携带嗜铬细胞瘤的动物尿中去甲肾上腺素和多巴胺的排泄量明显更高。然后，在嗜铬细胞瘤大鼠模型中研究钙拮抗剂硝苯地平的降压作用和抑制儿茶酚胺释放的作用，并与α肾上腺素受体拮抗剂吡嗪进行比较。当肿瘤变得可触及时，荷瘤动物被分配到不同的治疗组之一：单独嗜铬细胞瘤（未经治疗），盐酸哌唑嗪（1mg/kg/天）和硝苯地平（3mg/kg/天）。接种后8周，与对照组相比，未经治疗的大鼠明显高血压。硝苯地平降低血压的效果与普拉唑嗪相同。给药的嗜铬细胞瘤大鼠尿中儿茶酚胺的排泄量也同样增加。两组肿瘤中儿茶酚胺含量差异无统计学意义。结果提示硝苯地平和吡唑嗪均能有效降低嗜铬细胞瘤大鼠血压，但对嗜铬细胞瘤细胞释放儿茶酚胺无抑制作用。

First, we attempted to produce a rat model for pheochromocytoma. Ten- to twelve-week-old New England Deaconness Hospital (NEDH) rats were inoculated, subcutaneously in the interscapular region, with 0.5*10^6 pheochromocytoma cells (PC-12). After inoculation, tumors first became palpable after 3-4 weeks. Systolic blood pressue and heart rate elevations were first noted 5-6 weeks after inoculation. Urinary excretion of catecholamines was increased 4 weeks after inoculation. In paticular, urinary excretions of norepinephrine and dopamine were significantly higher in pheochromocytoma-bearing animals compared to controls.Then, the hypotensive effect, and the effect of inhibiting catacholamine release, of the calcium antagonist nifedipine, were studied in this rat model for pheochromocytoma, in comparision with the alpha adreneregic receptor antagonist prazosin. At the time tumors became palpable, tumor-bearing animals were assigned to one of various treatment groups : pheochromocytoma alone (untreated), prazosin hydrochloride (1mg/kg/day), and nifedipine (3mg/kg/day). Eight weeks following inoculation, the untreated rats were markedly hypertensive compared to controls. Nifidipine lowered blood pressure to the same degree that prazosin did. Urinary excretion of catecholamines was similarly increased in the pheochromocytoma rats administered the various drug regimens. Catecholamine contents in the tumors were not significantly different between them.The results suggests that both nifidipine and prazosin are effective in lowering blood pressure in pheochromocytoma rats, but they have no ability to inhibit catecholamine release from pheochromocytoma cells.