CENTRAL HYPOTENSIVE EFFECTS OF THE ALPHA(2A)-ADRENERGIC RECEPTOR SUBTYPE

alpha 2-Adrenergic receptors (alpha(2)ARs) present in the brainstem de crease blood pressure and are targets for clinically effective antihyp ertensive drugs. The existence of three alpha(2)AR subtypes, the lack of subtype-specific ligands, and the cross-reactivity of alpha(2)AR ag onists with imidazoline receptors has precluded an understanding of th e role of individual alpha(2)AR subtypes in the hypotensive response. Gene targeting was used to introduce a point mutation into the alpha 2 alpha AR subtype in the mouse genome. The hypotensive response to alp ha(2)AR agonists was lost in the mutant mice, demonstrating that the a lpha(2a)AR subtype plays a principal role in this response.