General Pharmacology: The Vascular System 1999-07-01

Characterization of postjunctional alpha-adrenoceptors in the pithed mouse.

G P McCafferty, D P Naselsky, J P Hieble

Index: Gen. Pharmacol. 33(1) , 99-105, (1999)

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Abstract

The adrenoceptor subtypes responsible for the pressor response to alpha1- and alpha2-adrenoceptor agonists have not yet been established, although gene knockout experiments in the mouse have provided evidence for a role of the alpha1B- and alpha2B-adrenoceptor. We have evaluated the blood pressure response to selective activation of postjunctional alpha1- and alpha2-adrenoceptors in the pithed mouse. The pressor response to phenylephrine was sensitive to blockade by terazosin, a selective alpha1-adrenoceptor antagonist, but insensitive to rauwolscine, an antagonist at alpha2-adrenoceptors. Phentolamine, a nonselective alpha-adrenoceptor antagonist, blocked the response to either phenylephrine or the selective alpha2-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 alpha1-adrenoceptor antagonist having no affinity for the alpha2B adrenoceptor, blocked the response to phenylephrine but not B-HT 933. Comparison of the potencies of these antagonists against the pressor response to phenylephrine with their affinities for recombinant alpha1-adrenoceptor subtypes suggests that this response is mediated by either alpha1B- or alpha1D-adrenoceptors. The alpha2B-adrenoceptor subtype is likely to take part in the response to B-HT 933. The ability of certain quinazoline alpha1-adrenoceptor antagonists to block the alpha2B adrenoceptor may contribute to their activity as antihypertensive agents.