Vasodilator proteins: role in delayed cerebral vasospasm.

Abstract:

: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.

journal_name

Stroke

journal_title

Stroke

authors

White RP

doi

10.1161/01.str.17.2.207

subject

Has Abstract

pub_date

1986-03-01 00:00:00

pages

207-13

issue

2

eissn

0039-2499

issn

1524-4628

journal_volume

17

pub_type

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