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      Central hypotensive effects of the alpha2a-adrenergic receptor subtype.

      Science (New York, N.Y.)
      Adrenergic alpha-2 Receptor Agonists, Adrenergic alpha-Agonists, pharmacology, Animals, Antihypertensive Agents, Base Sequence, Blood Pressure, drug effects, physiology, Brain Stem, Gene Targeting, Heart Rate, Imidazoles, Medetomidine, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Point Mutation, Quinoxalines, Receptors, Adrenergic, alpha-2, genetics, metabolism

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          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.

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