The long-term goals are to develop a better understanding of how the volatile anesthetic agents, isoflurane and halothane, attenuate the sympathetic vasoconstrictor tone in splanchnic and cutaneous capacitance veins. During stress, increase in sympathetic tone to these veins is a major mechanism by which large volumes of blood are shifted to the heart to enhance cardiac output. Interestingly, these very veins are among the first to dilate following inhalation of halothane or isoflurane. Thus anesthetics for patients who are hypovolemic or for patients whose cardiac output is being maintained through hyperactivity of the sympathetic nervous system. Because the portal venous system starts and ends with capillaries, direct measurement of pressures via catheter during anesthesia cannot be achieved noninvasively; thus information on the effects of anesthetics on this system lags behind that in other vessels. In vitro techniques can provide much information. Completed studies indicate that differences exist between various blood vessels in the """"""""dynamics"""""""" of norepinephrine (NE) at neuroeffector junctions and in the release of neuropeptide Y (NPY) and interactions between NPY and NE. Also, the ratios of released NPY to released NE are different in different vessels. Halothane (and also hypoxia) decreases the release of NPY (and NE) and the vesicular retention of NE. The proposed studies will determine in vitro whether differences exist between """"""""sensitive"""""""" and """"""""nonsensitive"""""""" vessels and will include: (a) a determination of the effects of halothane and isoflurane on indices of NE synthesis, vesicular retention of NE, release of NE, neuronal reuptake of NE, and on activity of monoamine oxidase (an enzyme responsible for degradation of NE); (b) a determination of the proportion of the response to neuronal stimulation that is attributable to NPY in normal vessels and the dependency of that response on the presence of endothelium; (c) the effects of halothane and isoflurane on postjunctional responses to NE and NPY. Radioimmunoassay will be used to measure NPY. High-performance liquid chromatography with electrochemical detection will be used to measure NE, its precursors, and its metabolites, which will provide indices of synthesis, vesicular retention, release, and reuptake of NE.
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