Altered release and metabolism of norepinephrine in superfused canine saphenous veins in the presence of halothane and hypoxia.
BACKGROUND
Hypoxia and halothane are both known to have different effects on the release and disposition of norepinephrine at sympathetic nerve terminals during neurotransmission. In adverse clinical situations, both conditions may be present, but the effects of halothane and hypoxia together are not known. Therefore, studies were made of the effects of low partial pressures of oxygen and of halothane on the release, action, and metabolism of norepinephrine at sympathetic nerve endings in isolated segments of a blood vessel in which halothane is known to affect norepinephrine release and action profoundly.


METHODS
Saphenous veins were removed from dogs, suspended for superfusion with Krebs-Ringer solution, and stimulated electrically. The veins were exposed to either 0%, 0.75%, or 1.5% halothane in the presence of 95% O2, 5% CO2, or 5% O2, 5% CO2, and 90% N2. Superfusates were collected under basal conditions, during and after electrical field stimulation, and poststimulation. Norepinephrine and its intraneuronal metabolite, 3,4-dihydroxyphenylglycol, were measured in superfusates and in the tissues after superfusion using high-performance liquid chromatography with electrochemical detection.


RESULTS
Halothane decreased 1) evoked release of norepinephrine, 2) contractile response of the smooth muscle to nerve stimulation, 3) formation of 3,4-dihydroxyphenylglycol, and 4) tissue content of norepinephrine. However, hypoxia 1) increased evoked release of norepinephrine but decreased 2) contractile response during nerve stimulation, 3) formation of 3,4-dihydroxyphenylglycol, and 4) tissue content of norepinephrine. When halothane and hypoxia were present together, their effects on 3,4-dihydroxyphenylglycol formation, tissue content of norepinephrine, and the contractile responses appeared to be additive, but norepinephrine release was decreased compared with control concentrations.


CONCLUSIONS
Although halothane and hypoxia had similar and additive effects on the intraneuronal metabolism of norepinephrine and on the postjunctional responses of smooth muscle to nerve stimulation, they had opposite effects on norepinephrine release from sympathetic nerve endings. The halothane-induced decrease in norepinephrine release overrode the increased release of norepinephrine caused by hypoxia.
Kamath
G S
GS
Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota 55905.
Rorie
D K
DK
Tyce
G M
GM
D000818:Animals; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006221:Halothane / Q000008:administration & dosage / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D012501:Saphenous Vein / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D014018:Tissue Distribution
D008734:Methoxyhydroxyphenylglycol; C010117:3,4-dihydroxyphenylglycol; D006221:Halothane; D009638:Norepinephrine