Direct coronary and cerebral vascular responses to dexmedetomidine. Significance of endogenous nitric oxide synthesis.
Dexmedetomidine activates alpha 2-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 alpha 2 receptors. The direct vasoconstrictor effects of alpha 2-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(-5) M and in the absence and presence of NG nitro-l-arginine methyl ester (L-NAME), an inhibitor of vascular nitric oxide synthesis. Dexmedetomidine (3 x 10(-8) to 3 x 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 alpha 2-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226.
M G
MG
Coughlan
J G
JG
Lee
Z J
ZJ
Bosnjak
W T
WT
Schmeling
J P
JP
Kampine
D C
DC
Warltier
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D020926:Medetomidine; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide; D014661:Vasoconstriction
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; C050701:atipamezole; D009569:Nitric Oxide; D001120:Arginine; D020926:Medetomidine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin