The central hypotensive effect induced by alpha 2-adrenergic receptor stimulation is dependent on endothelial nitric oxide synthase |
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Authors: | Feldman Josiane Fellmann Lyne Bousquet Pascal |
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Affiliation: | Laboratory of Neurobiology and Cardiovascular Pharmacology, INSERM U715, Faculty of Medicine, Louis Pasteur University, Strasbourg, France. |
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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. |
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