An in vivo model for the assessment of acute fibrinolytic capacity of the endothelium

Thromb Haemost. 1997 Oct;78(4):1242-8.


The effects on blood flow and plasma fibrinolytic and coagulation parameters of intraarterial substance P, an endothelium dependent vasodilator, and sodium nitroprusside, a control endothelium independent vasodilator, were studied in the human forearm circulation. At subsystemic locally active doses, both substance P (2-8 pmol/min) and sodium nitroprusside (2-8 microg/min) caused dose-dependent vasodilatation (p <0.001 for both) without affecting plasma concentrations of PAI-1, von Willebrand factor antigen or factor VIII:C activity. Substance P caused local increases in t-PA antigen and activity (p <0.001) in the infused arm while sodium nitroprusside did not. At higher doses, substance P increased blood flow and t-PA concentrations in the noninfused arm. We conclude that brief, locally active and subsystemic infusions of intraarterial substance P cause a rapid and substantial local release of t-PA which appear to act via a flow and nitric oxide independent mechanism. This model should provide a useful and selective method of assessing the in vivo capacity of the forearm endothelium to release t-PA acutely.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Flow Velocity / drug effects
  • Blood Pressure / drug effects
  • Brachial Artery
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiology*
  • Factor VIII / analysis
  • Fibrinolysis*
  • Forearm / blood supply
  • Humans
  • Injections, Intra-Arterial
  • Male
  • Nitroprusside / pharmacology
  • Plasminogen Activator Inhibitor 1 / analysis
  • Substance P / administration & dosage
  • Substance P / pharmacology*
  • Tissue Plasminogen Activator / metabolism*
  • Vasodilator Agents / pharmacology*
  • von Willebrand Factor / analysis


  • Plasminogen Activator Inhibitor 1
  • Vasodilator Agents
  • von Willebrand Factor
  • Nitroprusside
  • Substance P
  • Factor VIII
  • Tissue Plasminogen Activator