Abstract
The nature of the postsynaptic adrenoreceptor subtypes which mediate vasoconstriction in the mesenteric arterial bed of the rat was investigated using mixed and selective .alpha.1, .alpha.2 and .beta.-agonists and antagonists. Phenylephrine (PE) an .alpha.1-selective agonist and noradrenaline (NA) a mixed .alpha.1 and .alpha.2-agonist, produced a rise in perfusion pressure (vasoconstriction). The responses to NA remained stable with time whereas responses to PE considerably increased. UK14304 and .alpha.2-selective agonist at low doses (10-8-10-7 moles), caused small, slow contractions in most preparations. Repeated administration of these doses or slightly higher ones, desensitized the tissue to this compound but not to NA or PE. Finally, UK14304 given simultaneously with NA or PE, at doses higher than 5 .times. 10-7 moles, reduced contractions to the latter compounds and this effect was not altered by 10-7 M rauwolscine, an .alpha.2-selective antagonist. Prazosin, an .alpha.1-selective antagonist, as expected, reduced contractions to NA considerably at 10-10-10-8 M and abolished contractions to UK14304 at 2 .times. 10-9M. Rauwolscine, at 10-8 M, potentiated contractions to NA and at 10-6M reduced contractions to both NA and PE (when compared to time controls). When propranolol (10-6 M), a .beta.-antagonist was included in the perfusion fluid, rauwolscine no longer potentiated responses to NA but reduced them at all concentrations. Under the same conditions rauwolscine affected the responses to PE in a similar direction to that observed in the absence of propranolol. These results suggest that in the rat mesenteric arterial bed: a. rauwolscine exerts an effect additional to .alpha.2-adrenoreceptor antagonism. Modification of this effect by propranolol indicates an interaction between this effect of rauwolscine and the .beta.-adrenoreceptor. b. vasoconstriction in the mesenteric arterial bed of the rat is mainly mediated postsynaptically by .alpha.1-adrenoreceptors although the contribution of an .alpha.2-mediated component cannot be excluded. c. UK14304 is an .alpha.1-partial agonist as well as an .alpha.2-agonist.