Abstract
It has recently been shown that the pharmacological profile of α 1-adrenoceptors mediating constriction of porcine carotid arteriovenous anastomoses resembles that of α 1A- and α 1B-adrenoceptor subtypes. In an attempt to verify the involvement of α 1A-adrenoceptors, we used the potent α 1A-adrenoceptor agonist N-[5-(4,5-dihydro-1 H-imidazol-2yl)-2-hydroxy-5,6,7,8-tetrahydro-naphthalen-1-yl]methane sulphonamide (A61603) and found that intracarotid (i.c.) administration of A61603 (0.3–10 μg kg −1) dose-dependently decreased porcine carotid blood flow and vascular conductance. This decrease was exclusively due to a constriction of carotid arteriovenous anastomoses; the capillary blood flow and conductance remained unchanged. Surprisingly, the responses to A61603 were little modified by prior i.v. treatment with 5-methylurapidil (1000 μg kg −1), prazosin (100 μg kg −1) or a combination of prazosin and rauwolscine (100 and 300 μg kg −1, respectively). The 5-HT 1B/1D receptor antagonist N-[4-methoxy-3-(4-methyl-1-piperazinyl) phenyl]-2′-methyl-4′(5-methyl-1,2,4-oxadiazol-3-yl)[1,1,-biphenyl]-4-carboxamide hydrochloride monohydrate (GR127935; 500 μg kg −1) and ketanserin (500 μg kg −1) also failed to modify carotid vascular responses to A61603, but, interestingly, methiothepin (3000 μg kg −1) proved to be an effective antagonist. Taken together, the present results show that A61603 is a relatively poor agonist at the α 1A-adrenoceptor in anaesthetised pigs and that the carotid vasoconstriction produced by A61603 is mediated by a novel non-adrenergic mechanism.
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