Tachyphylaxis to phentolamine-induced hypotensive effect in rats

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.