In vivo characterization of B-2 receptors mediating hypotension in anesthetized rabbits and guinea pigs

With the discovery of suitable pharmacologic tools for B 2 receptor characterization, it has been demonstrated in vitro that the pharmacological spectrum of this receptor type obtained in various organs (e.g. intestine, vessels, urogenital tract) remains the same within the species but may show marked differences among species (e.g. the rabbit, the guinea pig) (Regoli et al., 1993; Regoli et al., 1994). Thus, orders of potency of agonists in rabbit and guinea pig tissues are opposite in that [Hyp3]BK is approximately 50- 100 times more potent than [AibT]BK in the rabbit and inversely, the latter compound is 2-10 times more active than [Hyp3]BK in the guinea pig. Furthermore, competitive antagonists, such as DArg[Hyp3,d-PheV,LeuS]BK and WIN 64338 (a nonpeptide compound), have also shown differences in their ability to block bradykinin responses in these two species while HOE 140, a non-competitive and long-acting antagonist, shows equipotent activities on both. Based on these results, we have suggested that B 2 receptors may be pharmacologically subject to interspecies variability. The present study was designed to find out if results obtained in vitro can be reproduced in vivo by measuring pharmacological parameters (namely EDs0 for agonists and ICso for antagonists) on kinin-induced blood pressure changes in the rabbit and the guinea pig.