Original ArticlesAdditional evidence that the sympathetic nervous system regulates the vessel wall release of tissue plasminogen activatorWang, Y.; Jiang, X.; Hand, A. R.; Gilles, C.; Kirk, J.; Cone, R. E.; O'Rourke, J.Author Information Y. Wang, X. Jiang, C. Gilles, R. E. Cone and J. O'Rourke are with the Department of Pathology, and A. R. Hand is with the Central Electron Microscope Facility, University of Connecticut Health Center, Farmington, Connecticutt, USA. (Received 2 October 2001; revised 4 January 2002; accepted 8 January 2002) Sponsorship: Supported by an American Heart Association grant in aid (REC), the Connecticut Lions Eye Research Foundation, and the Daniel M. and Lola H. Taylor Fellowship. Address correspondence to James O'Rourke, M.D., Department of Pathology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3105, USA. Tel: (+1) 860 679 3898; Fax: (+1) 860 679 2936; E-mail: O'Rourke@idx.uchc.edu Blood Coagulation & Fibrinolysis: September 2002 - Volume 13 - Issue 6 - p 471-481 Buy Abstract It is established that sympathetic neurons can synthesize, transport and store tissue plasminogen activator (t-PA) within axon terminals in the smooth muscle of vessel walls. Moreover, sympathetic excitations (e.g. physical and mental stress) are known to induce an acute release of t-PA into the circulation. However, relatively little is known about the nature and extent of sympathetic nervous system involvement in the release process per se. We inquired whether a chemical sympathectomy will alter the release of t-PA into the blood, and the intrinsic release of stored t-PA from isolated whole vessel explants. A long-term sympathectomy was induced in adult Sprague–Dawley rats by injection of guanethidine during a 5-week course. The destruction of ganglion neurons and vessel wall axons was verified immunohistochemically. t-PA release was assayed as the free activity in hind limb plasma and explant culture medium. Following sympathectomy: (i) the basal t-PA activity in plasma was 70% less than controls (2.92 ± 1.96 versus 9.33 ± 1.72 IU/ml;P ≤ 0.001); (ii) the acute release from isolated vessels induced by bradykinin or phenylephrine was comparably reduced; and (iii) the greatest reductions occurred in densely innervated small vessel explants. The results provide new support for an autonomic regulation of neural t-PA release into the vessel wall matrix and blood of densely innervated thin-walled microvessels. © 2002 Lippincott Williams & Wilkins, Inc.