Central hypotensive effects of the alpha(2a)-adrenergic receptor subtype

alpha 2-Adrenergic receptors (alpha(2)ARs) present in the brainstem decrease blood pressure and are targets for clinically effective antihypertensive drugs. The existence of three alpha(2)AR subtypes, the lack of subtype-specific ligands, and the cross-reactivity of alpha(2)AR agonists with imidazoline receptors has precluded an understanding of the 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 alpha(2)AR agonists was lost in the mutant mice, demonstrating that the alpha(2a)AR subtype plays a principal role in this response.