Summary
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 μg/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.
