Comparison of the inhibitory effects of antithrombin III, alpha 2-macroglobulin, and thrombin in human basilar arteries: relevance to cerebral vasospasm.

Isolated human basilar arteries were used in this study to evaluate the inhibitory effect of antithrombin III (AT III), thrombin, and alpha 2-macroglobulin (alpha 2-M) on contractions elicited by K+, serotonin (5-HT), prostaglandin (PG) D2, PGF2 alpha, and plasmin. alpha 2-M (0.5-1.0 mg/ml) failed to affect the contractions produced by contractile agonists significantly but did notably reduce the basal tone of the arteries. Thrombin (1 and 10 U/ml) reduced basal tone and significantly inhibited the contractions elicited by K+, PGF2 alpha, and plasmin. The relaxant effect of thrombin was abolished by procedures that destroy endothelium and by exposing the artery to thrombin for prolonged periods (tachyphylaxis). AT III (1-6 U/ml) reduced basal tone and significantly inhibited, in a concentration-dependent manner, the contractile responses to K+, 5-HT, PGD2, PGF2 alpha, and plasmin. In sharp contrast to thrombin, AT III did not induce tachyphylaxis nor was its vasorelaxant effect significantly reduced by destruction of the endothelium. The results show AT III to be a potent and nonspecific inhibitor of human cerebral arteries and support the hypothesis that AT III may contribute to the delay of cerebral vasospasm seen in patients who experience aneurysmal hemorrhage.