Role of plasmin, thrombin, and antithrombin III as etiological factors in delayed cerebral vasospasm.
The fibrinolytic enzyme plasmin at 0.25 units/ml produced a contraction of isolated canine basilar arteries that developed slowly and was sustained for at least 2 hours. Plasmin and thrombin (1 unit/ml) acted synergistically to enhance the contractile response. In contrast to plasmin, the marked contraction elicited by thrombin ended within 1 hour, and afterward the artery was completely tachyphylactic to thrombin. Fibrin clot, fibrinopeptides, and fibrin degradation products did not prolong significantly the effect of thrombin or prevent the tachyphylaxis. Plasmin and thrombin may occupy a common membrane receptor because exposing the artery briefly to trypsin (24 micrograms/ml) thereafter abolished the contractile effect of plasmin and thrombin without affecting the action of other agonists. Antithrombin III (1.0 unit/ml) relaxed basilar arteries that were precontracted with plasmin (0.5 unit/ml), thrombin (1.0 unit/ml), serotonin (10(-5) M), uridine triphosphate (10(-4) M), or KCl (8 X 10(-2) M). The results suggest that the vasoconstrictor effect of thrombin might contribute to hemostasis after subarachnoid hemorrhage (SAH) but, because of tachyphylaxis, not to delayed vasospasm. On the other hand, the constrictor action of plasmin might appear late in the course of SAH in association with clot lysis and tissue repair. Last, the level of the vasorelaxant antithrombin III in cerebrospinal fluid could control the appearance and severity of cerebral arterial spasm in SAH.
White
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Robertson
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JT
D015119:Aminocaproic Acid / Q000494:pharmacology; D000818:Animals; D000990:Antithrombin III / Q000494:pharmacology*; D007611:Aprotinin / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects; D004285:Dogs; D005260:Female; D005340:Fibrinogen / Q000494:pharmacology; D005341:Fibrinolysin / Q000494:pharmacology*; D002546:Ischemic Attack, Transient / Q000209:etiology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D013917:Thrombin / Q000494:pharmacology*; D013997:Time Factors; D014357:Trypsin / Q000494:pharmacology
D000990:Antithrombin III; D005340:Fibrinogen; D007611:Aprotinin; D014357:Trypsin; D013917:Thrombin; D005341:Fibrinolysin; D015119:Aminocaproic Acid