BJA Advance Access published online on November 5, 2008
British Journal of Anaesthesia, doi:10.1093/bja/aen316
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Effects of nitric oxide synthase inhibition on dexmedetomidine-induced vasoconstriction in healthy human volunteers
1 Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Itäinen Pitkäkatu 4B, FI-20520 Turku, Finland
2 Department of Anesthesia and Perioperative Medicine, University of California, San Francisco, CA, USA
3 GE Healthcare Finland Oy, POB 300, FI-00031 GE, Finland
4 Department of Anesthesiology and Intensive Care, Turku University Hospital, POB 52 FI-20521, Turku, Finland
* Corresponding author. E-mail: amir.snapir{at}utu.fi
Background: This study aimed to assess the contribution of endothelial nitric oxide synthesis to the net responses of human peripheral blood vessels in vivo to the selective 
2-adrenoceptor agonist dexmedetomidine.
Methods: Two groups of healthy young men were studied. In the first experiment, after brachial plexus block, the responses of digital arteries to systemically administered dexmedetomidine (target plasma concentration 1.2 ng ml–1) were studied using a photoplethysmograph (n=10) during i.a. infusions of saline and the nitric oxide synthase (NOS) inhibitor NG-monomethyl-L-arginine (L-NMMA) (8 µmol min–1). In a separate experiment, after pre-treatment with acetylsalicylic acid, responses to increasing doses of dexmedetomidine (0.01–164 ng min–1) in the presence and absence of L-NMMA were compared in dorsal hand veins (DHV) (n=10) using linear variable differential transformers.
Results: L-NMMA significantly augmented dexmedetomidine-induced vasoconstriction of digital arteries as assessed by an increase in light transmission through a finger and by a decrease in finger temperature. The mean (95% confidence interval) extent of the additional effect of L-NMMA over the constrictor effect of dexmedetomidine alone was 19% (14–24) (P<0.0001). In DHV, L-NMMA had variable effects on the dexmedetomidine-constriction dose–response curve. In three subjects, the curve was shifted significantly to the left (with a >10-fold difference in ED50), but ED50 was only marginally affected by L-NMMA in the other subjects (difference in ED50 <five-fold).
Conclusions: The endothelial NOS enzyme has a significant role in opposing the vasoconstrictor action of dexmedetomidine at drug concentrations within the therapeutic range.
Keywords: muscle vascular, pharmacology, responses; pharmacology, dexmedetomidine, nitric oxide; sympathetic nervous system, dexmedetomidine
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