Thrombin-Elicited Contractile Responses of Aortic Smooth Muscle

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Abstract
Human α-thrombin at physiologically relevant concentrations of 0.75 to 225 nM (0.01 to 22 clotting units/ml) caused rabbit thoracic aorta to slowly contract in isolated organ baths. Near maximum contractile tension (10% below the irreversible contraction caused by 22 units/ml) was slowly generated by 75 nM α-thrombin (8 units/ml) over 18 min and was 50% that of the norepinephrine (NE) control. The initial tonus could only be regained by repeated washing and 60 min equilibration. Tissues were refractory to a second 75 nM α-thrombin challenge but responded fully to 1.0 nM NE. Conversion of human α-thrombin to nonclotting but estero/amidolytically active 7-thrombin (M) of α-thrombin prior to contracting in response to higher concentrations during cumulative dose-response experiments. Our data suggest that catalytically active thrombin forms (α- or nonclotting β- and 7-thrombins) may have hemostatic functions at the vascular levels in hemostasis.