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

首先，我们试图建立一种大鼠嗜铬细胞瘤模型。将10~12周龄新英格兰执事医院(NEDH)大鼠接种0.5×10~(-6)个嗜铬细胞瘤细胞(PC-12)。接种后，肿瘤在3-4周后开始可触及。在接种后5-6周，首次观察到收缩压和心率升高。接种后4周尿儿茶酚胺排泄量增加。具体地说，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显著高于对照组。然后，研究了钙拮抗剂硝苯地平在嗜铬细胞瘤大鼠模型中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哌唑嗪进行了比较。当肿瘤变得可触及时，携带肿瘤的动物被分配到不同的治疗组中：单独治疗嗜铬细胞瘤(未治疗)、盐酸哌唑嗪(1 mg/kg/天)和硝苯地平(3 mg/kg/天)。接种8周后，未经处理的大鼠与对照组相比明显高血压。硝苯地平降低血压的程度与哌唑嗪相同。在接受不同药物治疗的嗜铬细胞瘤大鼠中，尿儿茶酚胺的排泄量也同样增加。结果表明，硝苯地平和哌唑嗪均能有效降低嗜铬细胞瘤大鼠的血压，但不能抑制嗜铬细胞瘤细胞中儿茶酚胺的释放。

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.