Additional evidence that the sympathetic nervous system regulates the vessel wall release of tissue plasminogen activator

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. 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; </= 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.