Characterization of postjunctional α-adrenoceptors in the pithed mouse

The adrenoceptor subtypes responsible for the presser response to alpha(1)- and alpha(2)-adrenoceptor agonists have not yet been established, although gene knockout experiments in the mouse have provided evidence for a role of the alpha(1B)- and alpha(2B)-adrenoceptor. We have evaluated the blood pressure response to selective activation of postjunctional alpha(1)- and alpha(2)-adrenoceptors in the pithed mouse. The presser response to phenylephrine was sensitive to blockade by terazosin, a selective alpha(1)-adrenoceptor antagonist, but insensitive to rauwolscine, an antagonist at alpha(2)-adrenoceptors. Phentolamine, a nonselective alpha-adrenoceptor antagonist, blocked the response to either phenylephrine or the selective alpha(2)-adrenoceptor agonist B-HT 933, whereas rauwolscine blocked only B-HT 933. A dose of terazosin effective against phenylephrine had no effect on B-HT 933; however, the B-HT 933 response was antagonized when the terazosin dose was increased tenfold. A high dose of doxazosin, an alpha(1)-adrenoceptor antagonist having no affinity for the alpha(2B) adrenoceptor, blocked the response to phenylephrine but not B-HT 933. Comparison of the potencies of these antagonists against the presser response to phenylephrine with their affinities for recombinant alpha(1)-adrenoceptor subtypes suggests that this response is mediated by either alpha(1B)- or alpha(1D)-adrenoceptors. The alpha(2B)-adrenoceptor subtype is likely to take part in the response to B-HT 933. The ability of certain quinazoline alpha(1)-adrenoceptor antagonists to block the alpha(2B) adrenoceptor may contribute to their activity as antihypertensive agents. (C) 1999 Elsevier Science Inc. All rights reserved.