Difference in the potency of α 2 ‐adrenoceptor agonists and antagonists between the pithed rabbit and rat

1 The subtypes of α‐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 α 2 ‐subtype, with corresponding responses in the rat. 2 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. 3 The responses to pressor nerve stimulation at low frequencies (< 1 Hz) could be reduced by prazosin, rauwolscine or imiloxan but those at a higher frequency could be reduced only by prazosin. 4 These results indicate that the responses to noradrenaline or to nerve stimulation are mediated by both α 1 ‐and α 2 ‐adrenoceptors. Low doses or frequencies have a proportionately greater component which is α 2 . 5 Responses to noradrenaline after prazosin (1 mg kg −1 ), were sufficiently sensitive to rauwolscine to be considered as predominantly α 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 α 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 α 2 ‐adrenoceptors mediating pressor responses in vivo , like those in other tissues in vitro , are different in rat and rabbit, with regard to antagonists.