ENFLURANE, HALOTHANE, AND ISOFLURANE ATTENUATE CONTRACTILE RESPONSES TO EXOGENOUS AND ENDOGENOUS NOREPINEPHRINE IN ISOLATED SMALL MESENTERIC VEINS OF THE RABBIT

Background: Volatile anesthetics exert both direct and indirect (neurally mediated) effects to produce splanchnic venodilation. These effects may result in clinically relevant hemodynamic changes. The present study examined the direct effects of isoflurane, halothane, and enflurane on rabbit mesenteric venous smooth muscle. Methods. Changes in isometric tension, in response to exogenous and endogenous norepinephrine, were measured in isolated mesenteric vein rings before and during the administration of volatile anesthetics. Results: Exogenous and electrically evoked endogenous norepinephrine produced an increase in tension with superimposed rhythmic oscillations in tension. The exogenous norepinephrine-induced increase in tension was augmented in the presence of N-nitro-L-arginine methyl ester (L-NAME, 5 X 10(-5) m). The oscillatory activity was not altered by L-NAME. The increase in isometric tension in response to electrical stimulation was inhibited by phentolamine (5 X 10(-6) m) and tetrodotoxin (3 X 10(-6) M). Equianesthetic (1 MAC) concentrations of isoflurane, halothane, and enflurane significantly attenuated contractile responses to exogenous and endogenous norepinephrine, with isoflurane demonstrating a more depressant effect than halothane or enflurane. Volatile anesthetics also suppressed the amplitude and frequency of oscillations in the control as well as L-NAME-treated veins. The inhibitory effects of volatile anesthetics on the oscillations were comparable to the effects of ryanodine, a specific blocker of calcium channels in sarcoplasmic reticulum. Conclusions. These results suggest that: 1) vascular endothelium, via endothelium-derived relaxing factor, modulates exogenous norepinephrine responses of the venous smooth muscle; 2) the oscillatory behavior of mesenteric veins may be attributed to calcium fluxes in the venous smooth muscle cells; and 3) the norepinephrine-dependent increases in contractile and oscillatory activity are attenuated more by isoflurane than halothane or enflurane. This indicates that volatile anesthetic-mediated splanchnic venodilation is, at least in part, due to a direct action on vascular smooth muscle as well as withdrawal of sympathetic tone.