A61603-induced vasoconstriction in porcine carotid vasculature: involvement of a non-adrenergic mechanism

It has recently been shown that the pharmacological profile of alpha (1)-ad renoceptors mediating constriction of porcine carotid arteriovenous anastom oses 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-1 H-imidazol-2 yl)-2-hydroxy-5,6,7,8-tetrahhydronaphthalen-1-yl]methane sulphonamide (A616 03) and found that intracarotid (i.c.) administration of A61603 (0.3-10 mug kg(-1)) dose-dependently decreased porcine carotid blood flow and vascular conductance. This decrease was exclusively due to a constriction of caroti d arteriovenous anastomoses; the capillary blood flow and conductance remai ned unchanged. Surprisingly, the responses to A61603 were little modified b y prior i.v. treatment with 5-methylurapidil (1000 mug kg(-1)), prazosin (1 00 mug kg(-1)) or a combination of prazosin and rauwolscine (100 and 300 mu g kg(-1), respectively). The 5-HT1B/1D receptor antagonist N-[4-melhoxy-3-( 4-methyl-1-piperazinyl) phenyl]-2 ' -methyl-4 ' (5-methyl-1,2,4-oxadiazoal- 3-yl)[1,l,-biphenyl]-4-carboxamide hydrochloride monohydrate (GR127935; 500 mug kg(-1)) and ketanserin (500 mug kg(-1)) also failed to modify carotid vascular responses to A61603, but, interestingly, methiothepin (3000 mug kg (-1)) proved to be an effective antagonist. Taken together, the present res ults show that A61603 is a relatively poor agonist at the alpha (1A)-adreno ceptor in anaesthetised pigs and that the carotid vasoconstriction produced by A61603 is mediated by a novel non-adrenergic mechanism. (C) 2001 Elsevi er Science B.V. All rights reserved.