Heparin prevents the vasodilating actions of protamine on human small mesenteric arteries

Despite the wide clinical use of protamine, the precise mechanisms of its hypotensive effects during reversal of heparin anticoagulation have not been elucidated fully. We, therefore, investigated the effects of protamine on isolated human small mesenteric arteries, both in the absence and presence of heparin, employing the isometric tension recording method. Protamine exerted vasodilating actions in the absence of heparin: 1) protamine (> or = 50 or 150 micrograms/mL) inhibited (P < 0.05) both norepinephrine (1 microM)- and high K+ (40 mM)-induced contractions in the presence of extracellular Ca2+ both in endothelium-intact and -denuded tissues; and 2) protamine inhibited (P < 0.05) norepinephrine (1 microM)-induced, but not caffeine (10 mM)-induced, contractions in the absence of extracellular Ca2+. Such vasodilating actions were blocked almost completely in the presence of heparin. We conclude that only protamine, but not a heparin-protamine complex, has a vasodilating action on the human arteries.