Characterization of α‐adrenoceptors in the vasculature of the canine nasal mucosa

Abstract

1 α-Adrenoceptors present in the vasculature of the nasal mucosa in β-adrenoceptor blocked dogs have been characterized pharmacologically using selective α₁- and α₂-adrenoceptor agonists and antagonists. 2 In pentobarbitone-anaesthetized dogs, intra-arterial (i.a.) administration of the selective α₁-agonists cirazoline and phenylephrine, the selective α₂-agonist UK-14,304 and the mixed α₁/α₂-agonists adrenaline, noradrenaline and oxymetazoline produced dose-related nasal vasoconstrictor responses (as measured by decreases in nasal cavity pressure). The rank order of agonist potency was adrenaline > oxymetazoline = UK-14,304 > noradrenaline > cirazoline > phenylephrine. 3 The nasal response to cirazoline was inhibited by the selective α₁-adrenoceptor antagonist prazosin but not by the new, potent selective α₂-adrenoceptor antagonist RX 811059. In contrast, UK-14,304 was inhibited only by RX 811059. Either prazosin or RX 811059 reduced the effect of the mixed agonist adrenaline. 4 In spinal dogs, the noradrenaline-evoked fall in nasal cavity pressure was reduced by either prazosin or RX 811059. Prazosin attenuated markedly the nasal vasoconstrictor response to electrical stimulation of postganglionic fibres emerging from the superior cervical ganglion (SNS) whereas RX 811059 was ineffective. Administration of the neuronal re-uptake inhibitor cocaine potentiated the effect of i.a. noradrenaline but reduced marginally the maximal response to SNS. After cocaine, RX 811059 enhanced the effect of SNS and attenuated the response to noradrenaline. Prazosin reduced effectively the responses to both SNS and noradrenaline after cocaine. Pretreatment with the α₂-agonist UK-14,304 did not affect the response to noradrenaline in the nasal cavity but evoked a persistent (up to 2 h) reduction in the response to SNS. RX 811059 antagonized the inhibitory effect of UK-14,304. 5 These results demonstrate that both postjunctional α₁- and α₂-adrenoceptors mediating vasoconstriction are present in the canine nasal mucosa. In addition, sympathetic neurones innervating the nasal mucosa are characterized by a very efficient re-uptake process and contain prejunctional α₂-adrenoceptors.