Presence of postsynaptic alpha 2-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 (10 microgram/kg intravenously) markedly antagonized responses to lumbar sympathetic stimulation, whereas responses to injected noradrenaline were largely unaffected. 2. In beta-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 alpha 2-adrenoreceptor-blocking agent, antagonized responses to the alpha 2-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 alpha 1- and alpha 2-adrenoreceptors are located postsynaptically. Furthermore the results suggest that neuronally released noradrenaline acts mainly upon alpha 1-adrenoreceptors, whereas exogenous noradrenaline acts upon alpha 1- and alpha 2-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.