title: The central hypotensive effect induced by alpha 2-adrenergic receptor stimulation is dependent on endothelial nitric oxide synthase.
abstract: OBJECTIVE
  The aim of the present study was to determine whether the central antihypertensive effect of drugs that act via central alpha 2-adrenergic receptors is mediated by the nitric oxide-ergic system.
  
  
  METHODS
  The hypotensive effects of dexmedetomidine, a 'pure' alpha2-adrenergic agonist, were compared in endothelial nitric oxide synthase knockout and wild-type control mice.
  
  
  RESULTS
  When injected intravenously (5 mug/kg) in wild-type mice, dexmedetomidine elicited a depressor response (60 +/- 4 to 34 +/- 1 mmHg, P < 0.05), but had no hypotensive effect in endothelial nitric oxide synthase (eNOS) knockout mice (84 +/- 7 to 84 +/- 7 mmHg, P > 0.05). In the presence of N-omega-nitro-L-arginine, a nonselective nitric oxide synthase (NOS) blocker that does not cross the blood-brain barrier, the hypotensive effect of dexmedetomidine was not abolished (Delta MAP = 21 +/- 2 mmHg vs. Delta MAP = 26 +/- 3 mmHg, P > 0.05).
  
  
  CONCLUSIONS
  It is concluded that the central cardiovascular effects of alpha 2-adrenergic agonists, such as dexmedetomidine, require an intact expression of eNOS within the brain. This study raises the interesting question of whether central eNOS itself might be considered as a target for new cardiovascular drugs regardless of any activation of alpha 2-adrenergic receptors.
authors.affiliation: Laboratory of Neurobiology and Cardiovascular Pharmacology, INSERM U715, Faculty of Medicine, Louis Pasteur University, Strasbourg, France.
authors.forename: Josiane
authors.initials: J
authors.lastname: Feldman
authors.forename: Lyne
authors.initials: L
authors.lastname: Fellmann
authors.forename: Pascal
authors.initials: P
authors.lastname: Bousquet
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000502:physiology*; D020927:Dexmedetomidine / Q000494:pharmacology*; D004195:Disease Models, Animal; D051379:Mice; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000502:physiology
chemical_list: D000316:Adrenergic alpha-Agonists; D018341:Receptors, Adrenergic, alpha-2; D020927:Dexmedetomidine; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse