Neurovascular Fibrinolysis: Sympathetic nerves release tissue plasminogen activator(t‐PA) into the blood and reduce its viscosity

Sympathetic stimulations increase blood t‐PA fibrinolytic activity and post‐ mortem capillary bleeding. These responses suggest that neural stimulated increases in t‐PA fibrinolyis may enhance capillary perfusion by reducing blood viscosity. The source of increased t‐PA activity that enters the blood during sympathetic excitations and its effects on viscosity remain unidentified However, the sympathetic nervous system (SNS) that densely innervates arterioles also synthesizes and systemically distributes active t‐PA. We therefore tested whether t‐ PA released from a stimulated SNS enters the blood and reduces viscosity. We first created a transgenic mouse whose genes for t‐PA and the green fluorescent protein (GFP) are fused and confined to the SNS. Biomarked SNS t‐PA and immunostained t‐PA anitgen were then shown co‐localized within SNS axons embedded in all artery types. SNS stimulations then consistently reduced blood viscosity measured in a new low volume oscillating viscometer. Following stimulations blood levels of the SNS t‐PA biomarker and the t‐PA enzyme were each raised more than 50% above controls. These observations offer the first in vivo evidence that t‐PA released from a stimulated SNS enters the blood and reduces its viscosity. The concept that viscosity and capillary perfusion are autonomically regulated during SNS excitations, and therefore subject to therapy may now be considered.