Phentolamine--an unexpected agonist in the rabbit

Phentolamine (0.1-10 microM) caused an anomalous rightward shift of the relationship between the number of electrical field pulses and tachycardia in the rabbit isolated right atrium. Phentolamine was apparently acting as a presynaptic agonist on sympathetic nerve endings to inhibit transmitter release. The effect was prevented by benextramine treatment and antagonized 10 fold by yohimbine (1 microM) but not by prazosin (0.1 microM). In ganglion-blocked (mecamylamine) conscious or anaesthetized rabbits, phentolamine (3-1000 micrograms kg-1) caused a dose-related rise in blood pressure that was antagonized by yohimbine (1 mg kg-1). These pressor and inhibitory cardiac sympathetic nerve effects of phentolamine are not found in similar preparations from the guinea-pig or rat. Therefore, these rabbit-specific agonist effects of phentolamine at sites similar to alpha 2-adrenoceptors make this drug unsuitable as an alpha-adrenoceptor antagonist in rabbits.