大鼠对酚妥拉明降压作用的快速耐受性

Tachyphylaxis to phentolamine-induced hypotensive effect in rats

作者反复给药诱导麻醉大鼠对酚妥拉明的降压作用产生快速耐受时,ED_(50)由41±9μg/kg增加到110±41μg/kg,E_(max)6.8±1.3 kPa下降至4.5±1.9kPa;清醒大鼠对反复iv酚妥拉明的降压作用亦呈明显的递减趋势.iv酚妥拉明耐受时,大鼠对硝普钠、硝苯吡啶和六甲溴胺仍保持原有的反应性,对哌唑嗪则具有交叉耐受性;其肛尾肌α-肾上腺素受体对去甲肾上腺素和酚妥拉明的pD_2和pA_2明显降低.提示酚妥拉明的快速耐受性与α-受体的脱敏有一定关系.

Phentolamine-induced tachyphylaxis in rats was investigated. The ED50 of the fell in blood pressure by iv phentolamine increased to 110±41μgAg from 41±9μgAg and the Emax decreased to 45± 1.9 kPa from 6.8 ± 1.3 kPa when tachyphylaxis was reached in anesthetized rats. A decreasing trend in sensitivity to phentolamine was derived as the drug was iv administered repeated to conscious rats. A cross tachyphylaxis occurred to phentolarnine and prazosin, but not to sodium nitroprusside, niiedipine or hexamethonium bromide. The a-adrenergic receptors in the anococcygeal muscle of the phentolamine tachyphylactic rats exhibited low pD2 to noradrenaline and low pA, to phentolamine. These results support the concept that alpha receptors may play a major role in the process leading to an induced tachyphylaxis to phentolamine.