Vasodilation due to urokinase in the canine femoral circulation

Based upon clinical observations, we hypothesize that the plasminogen activator urokinase is vasoactive in addition to being fibrinolytic and thrombolytic. The effects of intra-arterial injections and infusions of urokinase were investigated in the canine femoral circulation. Injections of human urine urokinase increased femoral artery blood flow in a dose-related fashion that was not significantly attenuated by beta adrenergic blockade, antihistamine treatment, heating, atropine treatment or kallikrein inactivation. The Ploug preparation of urine urokinase was somewhat more effective than the Abbott or Sterling-Winthrop preparations in causing this dilation. Some nonspecific inhibition of the vasodilator responses was produced by inhibition of plasminogen activation with epsilon-aminocaproic acid. The continuous infusion of urokinase increased femoral arterial flow but there was some tendency to escape. Further experiments seem indicated to determine potential application of local urokinase in clinical conditions where vasodilation and fibrinolysis-thrombolysis might be of value.