HEPARIN PREVENTS THE VASODILATING ACTIONS OF PROTAMINE ON HUMAN SMALLMESENTERIC-ARTERIES

Despite the wide dinical use of protamine, the precise mechanisms Of i ts 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 ab sence and presence of heparin, employing the isometric tension recordi ng method. Protamine exerted vasodilating actions in the absence of he parin: 1) protamine (greater-than-or-equal-to 50 or 150 mug/mL) inhibi ted (P < 0.05) both norepinephrine (1 muM)- and high K+ (40 mM)-induce d contractions in the presence of extracellular Ca2+ both in endotheli um-intact and -denuded tissues; and 2) protamine inhibited (P < 0.05) norepinephrine (1 muM)-induced, but not caffeine (10 mM)-induced, cont ractions in the absence of extracellular Ca2+. Such vasodilating actio ns were blocked almost completely in the presence of heparin. We concl ude that only protamine, but not a heparin-protamine complex, has a va sodilating action on the human arteries.