Abstract

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