Original Articles
Blood Coagulation & Fibrinolysis. 13(6):471-481, September 2002.Wang, Y.; Jiang, X.; Hand, A. R.; Gilles, C.; Kirk, J.; Cone, R. E.; O'Rourke, J.
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.