Difference in the potency of alpha 2-adrenoceptor agonists and antagonists between the pithed rabbit and rat

Abstract

The subtypes of alpha-adrenoceptors which mediate pressor responses to sympathomimetic agonists or to nerve stimulation in pithed rabbits have been classified according to the effects of 'selective' antagonists and a comparison has been made, for the alpha 2-subtype, with corresponding responses in the rat. In the rabbit the dose-response curve for phenylephrine was shifted to the right in parallel by prazosin (1 mg kg-1) and was unaffected by rauwolscine (1 mg kg-1). The dose-response curve for noradrenaline was shifted to the right by prazosin (1 mg kg-1) and was shifted to a smaller extent by rauwolscine (1 mg kg-1) or imiloxan (10 mg kg-1). After rauwolscine, prazosin produced a rightward shift larger than when given alone. After prazosin, rauwolscine produced a rightward shift larger than when given alone. The responses to pressor nerve stimulation at low frequencies (less than 1 Hz) could be reduced by prazosin, rauwolscine or imiloxan but those at a higher frequency could be reduced only by prazosin. These results indicate that the responses to noradrenaline or to nerve stimulation are mediated by both alpha 1- and alpha 2-adrenoceptors. Low doses or frequencies have a proportionately greater component which is alpha 2. Responses to noradrenaline after prazosin (1 mg kg-1), were sufficiently sensitive to rauwolscine to be considered as predominantly alpha 2. A comparison was therefore made of such responses in the rat and rabbit. They were produced by a lower dose per unit body weight in the rat whereas this was less marked for the alpha 2-adrenoceptor agonist guanabenz. In the rabbit they were more susceptible to blockade by rauwolscine but were less sensitive to Wy 26703 than in the rat. This demonstrates that the alpha 2-adrenoceptors mediating pressor responses in vivo, like those in other tissues in vitro, are different in rat and rabbit, with regard to antagonists.