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.

No abstract

No abstract

In the isolated perfused hindlimb preparation of the dog, pressor responses to norepinephrine (NE) are mediated by postsynaptic alpha 1- and alpha 2-adrenergic receptors. Results obtained using preferential alpha 1- and alpha 2-adrenergic receptor antagonists suggest that the alpha 1-subtype is predominantly innervated while both alpha 1- and alpha 2-adrenergic receptor subtypes in vascular smooth muscle are accessible to circulating agonists and antagonists. Preliminary studies in the isolated perfused cat spleen support these in vivo findings in the dog. In contrast to vascular smooth muscle, the cat nictitating membrane appears to contain only alpha 1-adrenergic receptors postsynaptically.

The selective a2-adrenoceptor antagonist, RX78 1094, evoked a dose-related pressor response in the pithed rat preparation when administered in bolus doses by the intravenous route. This response was enhanced following depletion of endogenous amines by reserpine, and inhibited by the selective al-adrenoceptor antagonist, prazosin. Two other selective a2-adrenoceptor antagonists, Wy 26703 and Wy 26392, had no marked effect on the blood pressure of this preparation. Pretreatment of the preparation with Wy 26703 had no significant effect on the pressor response evoked by RX781094.It is concluded that RX78 1094 is an ocladrenoceptor agonist at similar doses to those at which it exhibits x2-adrenoceptor antagonist properties. The agonist activity exhibited by RX78 1094 is not a general property of all c2-adrenoceptor antagonists and should be considered when this compound is employed as an c2-adrenoceptor antagonist.