I-022

It has recently been shown that the pharmacological profile of alpha(1)-adrenoceptors mediating constriction of porcine carotid arteriovenous anastomoses resembles that of alpha(1A)- and alpha(1B)-adrenoceptor subtypes. In an attempt to verify the involvement of alpha(1A)-adrenoceptors, we used the potent alpha(1A)-adrenoceptor agonist N-[5-(4,5-dihydro-1H-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 microg 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 microg kg(-1)), prazosin (100 microg kg(-1)) or a combination of prazosin and rauwolscine (100 and 300 microg 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 microg kg(-1)) and ketanserin (500 microg kg(-1)) also failed to modify carotid vascular responses to A61603, but, interestingly, methiothepin (3000 microg kg(-1)) proved to be an effective antagonist. Taken together, the present results show that A61603 is a relatively poor agonist at the alpha(1A)-adrenoceptor in anaesthetised pigs and that the carotid vasoconstriction produced by A61603 is mediated by a novel non-adrenergic mechanism.