We will test the hypothesis that intense activation of the sympathetic nervous system (SNS) may cause an increase in pulmonary microvascular permeability to fluid and proteins. This question is of interest, because recent studies have suggested that an increased permeability might contribute to the development of neurogenic pulmonary edema, a form of edema which often occurs after central nervous system injury which evokes a massive centrally-mediated discharge of the SNS. Our basic approach will be to determine if the capability of the pulmonary microvasculature to sieve proteins relative to water during extravascular fluid filtration becomes impaired under these conditions. Alterations in this capability will be evaluated by analyzing changes in lymph flow and lymph protein concentration that may occur in an in situ canine lung preparation in which pure pre-nodal lung lymph will be collected. The normal capability of the microvasculature to sieve proteins will be evaluated in a control group of animals in which fluid filtration has been increased by raising left atrial pressure mechanically. Changes in lymph flow and lymph protein concentration occurring under these conditions will be compared with those observed in groups of animals in which the SNS has been stimulated either centrally or peripherally. Central stimulation will be evoked by intracranial drug administration (veratrine and tityustoxin) and by intracranial pressure elevation. Stellate ganglion and splanchnic nerve stimulation will be used to activate components of the SNS peripherally. The specific role of adrenergic receptors and the adrenal gland in mediating the changes in lung transvascular fluid and protein flux that occur in response to these stimuli will be further delinated by evaluating additional groups of animals following either Alpha-adrenergic blockade or adrenalectomy.
