Presence of Postsynaptic α2-Adrenoreceptors of Predominantly Extrasynaptic Location in the Vascular Smooth Muscle of the Dog Hind Limb

Abstract

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.

Evidence for neuro‐effector transmission through postjunctional α2‐adrenoceptors in human saphenous vein

“…(Stevens & Moulds, 1981;Glusa & Markwardt, 1983;Steen et al, 1984). Evidence that endogenous noradrenaline neurotransmitter acts on postjunctional M2-receptors has proved difficult to obtain even in animal experiments (see Docherty & Starke, 1982) or has proved negative (see Langer et al, 1980;Wilffert et al, 1982).…”

Vasoconstriction with norepinephrine causes less forearm insulin resistance than a reflex sympathetic vasoconstriction.

“…The evidence in animals of the existence of extrajunctional a 2 -receptors, which in addition to their effect on the modulation of neurotransmitter release also mediate vasoconstriction, 34 -35 has also been extended to humans. In human vasculature, locally released norepinephrine (by lower body negative pressure and by tyramine infusion) has a different functional effect than infused norepinephrine.…”

Characterization of the α‐adrenoceptors in the female rabbit urethra

“…Functional studies on isolated vascular smooth muscle suggest the existence of postjunctional aladrenoceptors in, e.g., the rat portal vein (Ruffolo et al, 1981), postjunctional a2-adrenoceptors in the feline middle cerebral artery (Skarby et al, 1983), and both of these subtypes postjunctionally in canine saphenous vein (De Mey & Vanhoutte, 1981) and feline lingual arteries (Skarby et al, 1983). Moreover, postjunctional al-and a2-adrenoceptors have been suggested to be involved in the pressor responses to a-adrenoceptor agonists in the pithed rat (Timmermans & van Zwieten, 1980) and dog (Constantine et al, 1980), and in the autoperfused hindlimb of the dog (Langer et al, 1980).…”