Presence of Postsynaptic a2-Adrenoreceptors of Predominantly Extrasynaptic Location in the Vascular Smooth Muscle of the Dog Hind Limb

1. In the autoperfused hind limb of the dog prazosin (10µg/kg intravenously) markedly antagonized responses to lumbar sympathetic stimulation, whereas responses to injected nor-adrenaline were largely unaffected. 2. In ß-adrenoreceptor- and ganglion-blocked animals, the hind limb pressor responses to phenylephrine were antagonized to a greater degree by prazosin than responses to injected noradrenaline. 3. Rauwolscine, a selective a2-adrenoreceptor-blocking agent, antagonized responses to the a2-adrenoreceptor agonist guanabenz, but not those to phenylephrine. 4. Hind limb pressor responses to noradrenaline were significantly inhibited by rauwolscine and further reduced by prazosin. 5. These results demonstrate that in this vascular bed a1- and a2-adrenoreceptors are located postsynaptically. Furthermore the results suggest that neuronally released noradrenaline acts mainly upon a1-adrenoreceptors, whereas exogenous noradrenaline acts upon a1- and a2-adrenoreceptors. 6. It is suggested that this selectivity of prazosin in blocking the vasoconstriction to neuronally-released noradrenaline may in part explain the effectiveness of this drug as an antihypertensive agent.