Difference in the potency of α₂‐adrenoceptor agonists and antagonists between the pithed rabbit and rat

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 α₂‐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 (< 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 α₁‐and α₂‐adrenoceptors. Low doses or frequencies have a proportionately greater component which is α₂. Responses to noradrenaline after prazosin (1 mg kg⁻¹), were sufficiently sensitive to rauwolscine to be considered as predominantly α₂. 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 α₂‐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 α₂‐adrenoceptors mediating pressor responses in vivo, like those in other tissues in vitro, are different in rat and rabbit, with regard to antagonists. 1987 British Pharmacological Society