Pharmacodynamic effects of tosyl-arginine methyl ester (TAME) on isolated human arteries

1. The effects of the competitive proteinase inhibitor TAME on isolated human umbilical and basilar arteries were studied. 2. Most experiments were performed on umbilical arteries and showed that 5 x 10(-4) M or 5 x 10(-3) M TAME significantly inhibited contractions elicited by prostaglandin F2 alpha, bradykinin, serotonin, and histamine. The inhibition was not endothelium-dependent. 3. The contraction elicited by prostaglandin E2 in basilar arteries was inhibited by TAME in a dose-dependent manner indicating that inhibition did not depend on the origin of the vessel. 4. Inhibition by 5 x 10(-7) M TAME of the contraction produced by KCl in the basilar artery was limited to low concentrations of KCl (10 and 30 mM). TAME did not significantly inhibit contractions of umbilical arteries to KCl. 5. At 5 U/ml (approximately 8.6 x 10(-8) M) antithrombin III markedly inhibited contractions of basilar arteries to prostaglandin E2 but had no effect of contractions elicited by 10(-6) M serotonin in the umbilical artery, nor did aprotinin (5 x 10(-4) M). 6. Although vessels of different origin may differ in sensitivity, the manifest effect of antiproteinases on arteries is inhibition.