The effect of halothane on norepinephrine responsiveness in rabbit small mesenteric veins.
The effect of halothane on the response of small isolated mesenteric capacitance veins to exogenous norepinephrine and electrically induced endogenous norepinephrine release was studied. The role of extra- and intracellular Ca2+ in norepinephrine-induced contractions was also examined. Two-millimeter-long segments from the second-order branch of the mesenteric vein were stretched to twice their resting diameter, and the generated tension was measured with a force transducer. Dose-dependent effects of norepinephrine on generated tension were examined before and after exposure to 0.75 and 1.5% halothane. (These concentrations produced perfusate halothane concentrations of 0.31 and 0.49 mM respectively.) Norepinephrine produced an increase in the basal vessel tension along with a superimposed rhythmic oscillation in tension. Although the magnitude of the tension increase was not affected by either concentration of halothane, the amplitude of the oscillations was reduced. Ryanodine (a blocker of Ca2+ release from the sarcoplasmic reticulum), like halothane, decreased the amplitude of the oscillations, but did not affect overall tension development. In the Ca2(+)-free medium the contractile response to norepinephrine was greatly attenuated as compared to control, whereas the oscillatory behavior was completely abolished. Norepinephrine release was examined indirectly by measuring the increase in tension during electric field stimulation. Response to endogenously released norepinephrine was significantly decreased by exposure to halothane 1.5% (0.49 mM) and blocked by pretreating the vessel with phentolamine. At concentrations used clinically, halothane did not affect overall developed tension in response to exogenously applied norepinephrine. However, 1.5% (0.49 mM) halothane decreased both sarcoplasmic-reticulum-dependent oscillations in tension and electrically induced release of endogenous norepinephrine.
Marijic
J
J
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226.
Madden
J A
JA
Kampine
J P
JP
Bosnjak
Z J
ZJ
D000818:Animals; D002118:Calcium / Q000502:physiology; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D008642:Mesenteric Veins / Q000187:drug effects / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D011817:Rabbits
D002118:Calcium; D006221:Halothane; D009638:Norepinephrine