Direct coronary and cerebral vascular responses to dexmedetomidine : significance of endogenous nitric oxide synthesis

Dexmedetomidine activates α2-adrenergic receptors in the central nervous system and in the peripheral vasculature. In vivo dexmedetomidine has been found to cause alterations in coronary and cerebral blood flows and arterial pressure by stimulation of vascular smooth muscle α2receptors. The direct vasoconstrictor effects of α2-adrenergic agonists may be opposed by release of endothelium-derived relaxing factor believed to be nitric oxide. A functional endothelium was demonstrated recently in canine coronary collateral vessels. The objective of the current study was to assess the direct effect of dexmedetomidine on isolated canine proximal and distal coronary arteries, coronary collateral vessels, and middle cerebral arteries. Responses were measured in tissue baths in the presence of indomethacin 10−5M and in the absence and presence of NG nitro-1-arginine methyl ester (L-NAME), an inhibitor of vascular nitric oxide synthesis. Dexmedetomidine (3 × 10−8 to 3 × 10−3.9) M) caused constriction (3.9, 5.5, 72.8, and 2.3% for proximal and distal coronary arteries, middle cerebral arteries, and coronary collateral vessels, respectively, expressed as a percentage of KCl-induced contraction) in all vessels. This constriction was enhanced by the presence of L-NAME in all vessels except cerebral arteries. The selective α2-adrenergic antagonist atipamezole (10−4 M) abolished the response to low but not high concentrations of dexmedetomidine in middle cerebral arteries, proximal coronary arteries, and coronary collateral vessels. The response to high concentrations of dexmedetomidine in distal coronary arteries also was abolished by atipamezole. In all other vessels studied, atipamezole only partially antagonized the vasoconstrictor effect of high doses of dexmedetomidine, possibly indicating different mechanisms of action at these concentrations. These results suggest that dexmedetomidine possesses direct vasoconstrictor effects in a variety of isolated vessels. These actions are modulated by vascular nitric oxide synthesis in coronary arteries and coronary collateral vessels but not in middle cerebral arteries.