title: Central hypotensive effects of the alpha2a-adrenergic receptor subtype.
abstract: alpha2-Adrenergic receptors (alpha2ARs) present in the brainstem decrease blood pressure and are targets for clinically effective antihypertensive drugs. The existence of three alpha2AR subtypes, the lack of subtype-specific ligands, and the cross-reactivity of alpha2AR agonists with imidazoline receptors has precluded an understanding of the role of individual alpha2AR subtypes in the hypotensive response. Gene targeting was used to introduce a point mutation into the alpha2aAR subtype in the mouse genome. The hypotensive response to alpha2AR agonists was lost in the mutant mice, demonstrating that the alpha2aAR subtype plays a principal role in this response.
authors.affiliation: Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: L B
authors.initials: LB
authors.lastname: MacMillan
authors.forename: L
authors.initials: L
authors.lastname: Hein
authors.forename: M S
authors.initials: MS
authors.lastname: Smith
authors.forename: M T
authors.initials: MT
authors.lastname: Piascik
authors.forename: L E
authors.initials: LE
authors.lastname: Limbird
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001483:Base Sequence; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001933:Brain Stem / Q000502:physiology; D000068438:Brimonidine Tartrate; D018390:Gene Targeting; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D020926:Medetomidine; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D017354:Point Mutation; D011810:Quinoxalines / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C547769:Adra2a protein, mouse; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D000068438:Brimonidine Tartrate; D020926:Medetomidine