Role of Sympathetic Postganglionic Neurons in Synovial Plasma Extravasation induced by Bradykinin. Jia-Pei Miao, Frederick, Wilfrid J[umlaut]anig, Jon D. Levine. Departments of Medicine, Anatomy, and Oral and Maxillofacial Surgery, University of California at San Francisco, Schools of Medicine and Dentistry, San Francisco, CA 94143-0452A, USA, Physiologisches Institut, Christian- Albrechts-Universit[umlaut]at zu Kiel, Germany.
APStracts 2:0286N, 1995.
SUMMARY AND CONCLUSIONS
1. Plasma extravasation through the endothelium of blood vessels is an integral component of the inflammatory response and dependent to a large extent on the inflammatory mediator bradykinin. We studied plasma extravasation induced by bradykinin perfusion (BK-induced PE) of the rat knee joint before and after various interventions that affect the sympathetic supply to the knee joint. We tested the hypothesis that plasma extravasation is dependent on the local sympathetic terminal supply to the synovia but not directly dependent on more proximal activity in the sympathetic neurons. As a control we used plasma extravasation induced by platelet activating factor (PAF) which acts directly on the endothelium of the blood vessels, that is, its action is independent of any innervation. Plasma extravasation into the knee joint cavity was determined spectrophotometrically by measuring, over time, the concentration of Evans blue dye extravasation into the joint perfusate following its intravenous injection. 2. Surgical sympathectomy at the lumbar level (L 2 -L 4 ), performed 4 and 14 days previously, reduced BK- induced PE by about 55-70%. 3. Decentralization of the lumbar sympathetic chain (cutting the preganglionic axons which innervate the postganglionic neurons to the hindlimb), interruption of the lumbar sympathetic chain during infusion of BK or co-perfusion of tetrodotoxin into the knee joint cavity did not reduce BK-induced PE. All three interventions abolish the activity in the sympathetic neurons but leave the peripheral postganglionic terminals in the joint capsule intact. 4. Surgical sympathectomy and decentralization did not affect plasma extravasation induced by intra-articular perfusion with PAF. 5. Electrical stimulation of the lumbar sympathetic chain at frequencies of 0.25 to 5 Hz, which probably also significantly decreases blood flow through the joint capsule, reduced basal plasma extravasation, BK-induced PE and PAF- induced PE. This reduction was frequency-dependent and was almost maximal at a stimulation frequency of 1 Hz. 6. In conclusion, BK-induced PE into the rat knee joint is dependent on the presence of intact sympathetic postganglionic nerve terminals innervating the joint capsule and not directly dependent on excitation of these neurons. However, electrical stimulation of the sympathetic neurons reduces the level of plasma extravasation, presumably due to vasoconstriction and decrease of blood flow through the joint capsule. These results indicate that peripheral action of inflammatory mediators on terminals of sympathetic neurons produces a facilitative effect on vascular permeability while centrally generated excitation of these neurons, which depresses blood flow (vasoconstrictor function), decreases plasma extravasation. The effect on blood flow is presumed to occur at the precapillary resistance vessels by vesicular release of transmitter(s). The facilitative effect on permeability occurs at the venules and includes inflammatory-mediator-stimulated, non-vesicular-dependent, production and release of a chemical substance (probably prostaglandin E 2 ). Whether both functions are represented in the same class of sympathetic postganglionic neuron or in distinct ones remains to be elucidated. 

Received 31 March 1995; accepted in final form 11 September 1995.
APS Manuscript Number J214-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 31 October 95