McGonigle R J, Brookins J, Pegram B L, Fisher J W
J Pharmacol Exp Ther. 1987 May;241(2):428-32.
In order to determine the influence of calcium on erythropoietin release in response to hypoxia, the effects of the calcium entry blocker verapamil on erythropoietin production were investigated. Hypoxia was induced in male Sprague-Dawley rats by placing them in a hypobaric chamber at 0.42 atmospheres for 6 and 12 hr. Serum levels of erythropoietin were measured by the exhypoxic polycythemic mouse bioassay and a sensitive radioimmunoassay for erythropoietin. Verapamil (5, 10 and 20 mg/kg i.p.) produced significant increases in mean serum erythropoietin levels after 6 and 12 hr of hypoxia, which was significantly higher than those of saline-injected hypoxic control rats. Mean arterial blood pressure values in rats injected with 5 and 10 mg/kg of verapamil were not significantly different from the preinjection controls when measured at ambient pressure over a 12-hr period. A dosage of 20 mg/kg of verapamil i.p. in rats produced a significant decrease in mean arterial pressure between 5 and 30 min after injection but was not significantly different from the vehicle controls between 30 min and 12 hr postinjection. In conclusion, the calcium entry blocker verapamil enhanced erythropoietin production in response to hypoxia. Thus, it is postulated that calcium plays a significant role in erythropoietin production and/or release.
为了确定钙对缺氧时促红细胞生成素释放的影响，研究了钙通道阻滞剂维拉帕米对促红细胞生成素产生的作用。将雄性Sprague-Dawley大鼠置于0.42个大气压的低压舱中6小时和12小时，以诱导缺氧。通过低氧性红细胞增多症小鼠生物测定法和一种灵敏的促红细胞生成素放射免疫测定法来测量血清促红细胞生成素水平。维拉帕米（腹腔注射5、10和20mg/kg）在缺氧6小时和12小时后使平均血清促红细胞生成素水平显著升高，显著高于注射生理盐水的缺氧对照大鼠。在12小时的常压测量期间，注射5mg/kg和10mg/kg维拉帕米的大鼠的平均动脉血压值与注射前对照无显著差异。腹腔注射20mg/kg维拉帕米的大鼠在注射后5至30分钟平均动脉压显著降低，但在注射后30分钟至12小时与溶媒对照无显著差异。总之，钙通道阻滞剂维拉帕米增强了对缺氧的促红细胞生成素产生。因此，推测钙在促红细胞生成素的产生和/或释放中起重要作用。
