Vasodilator proteins: role in delayed cerebral vasospasm.
Blood proteins could play a critical role in the pathogenesis of cerebral vasospasm in subarachnoid hemorrhage (SAH) as agonists and as antagonists of vasoconstriction. The present study was designed primarily to quantify the inhibition produced by antithrombin III of the phasic responses elicited by cumulative doses of KCl, serotonin (5-HT), uridine triphosphate (UTP), and thrombin in isolated canine basilar arteries, and to ascertain whether other proteins might act similarly. Antithrombin III (1 unit/ml and 3 units/ml) given 2 min beforehand inhibited all agonists. The inhibition was not dependent on a functional endothelium nor due to stimulation of the electrogenic sodium pump. Alpha2-macroglobulin (0.1 mg/ml and 0.4 mg/ml) inhibited the contractile responses to high K+, 5-HT and thrombin. Kallikrein (1 and 4 units/ml) did not inhibit UTP but inhibited high K+ and 5-HT through an effect on the endothelium. Kallikrein (1 unit/ml) irreversibly blocked the responses to thrombin. Globulins (3 mg/ml) and fibrinogen (0.3 mg/ml) were not inhibitory. The results demonstrate that anticoagulant proteins are very effective nonspecific inhibitors of the vasoconstriction, whereas the serine protease kallikrein selectively blocks thrombin. The remarkable potency of antithrombin III suggests that it may protect cerebral arteries from exhibiting vasospasm in SAH.
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D000818:Animals; D000990:Antithrombin III / Q000494:pharmacology; D001798:Blood Proteins / Q000502:physiology*; D002536:Cerebral Arteries / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005916:Globulins / Q000032:analysis; D002546:Ischemic Attack, Transient / Q000209:etiology*; D007610:Kallikreins / Q000494:pharmacology; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013345:Subarachnoid Hemorrhage / Q000150:complications; D013917:Thrombin / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology; D014661:Vasoconstriction; D014664:Vasodilation; D000511:alpha-Macroglobulins / Q000494:pharmacology
D001798:Blood Proteins; D005916:Globulins; D000511:alpha-Macroglobulins; D012701:Serotonin; D011189:Potassium Chloride; D000990:Antithrombin III; D005340:Fibrinogen; D007610:Kallikreins; D013917:Thrombin; D014544:Uridine Triphosphate