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Korean J Anesthesiol > Volume 33(4); 1997 > Article
Korean Journal of Anesthesiology 1997;33(4):591-603.
DOI: https://doi.org/10.4097/kjae.1997.33.4.591   
The Vasodilation of Protamine and the Influence of Heparin on its Actions in the Isolated Aortic Arteries of Rats.
Seok Hwa Yoon, Yoon Hee Kim, Sung Bum Kwon, Jung Eun Lee, Hai Ja Kim, Sae Jin Choi
Abstract
BACKGROUND
When used to reverse the anticoagulant effect of heparin, protamine administration after cardiovascular bypass often can lead to systemic hypotension. During the reversal of heparin-induced anticoagulation, the effects of protamine on both a heparin-protamine complex and free protamine on the cardiovascular system should be considered.
METHOD
To determine whether the hypotensive effect of heparin-protamine and/or protamine could be caused by endothelium-dependent and-independent component, we studied rings of the arotic arteries in rats suspended in organ chambers containing Tris Tyrode solution at 37oC and 100% O2. Arterial rings with or without endothelium were contracted with 40 mM KCl or 3 +/- 10-6M phenylephrine and then exposed to increasing concentrations of protamine (final organ bath concentration, 40~400 g/ml) both in the absence and presence of heparin (200 U/ml).
RESULTS
Protamine induced concentration-dependent relaxation in arterial rings with endothelium, which were significantly greater than in rings without endothelium. The endothelium-dependent relaxation induced by protamine was inhibited by NG-monomethyl-L-arginine (L-NMMA) (10-5M) pretreatment, but was not inhibited by indomethacin (3x10-6M) pretreatment on rings with endothelium. Furthermore, the contractile inhibition was enhanced by superoxide dismutase (100 U/ml). Also, such vasodilating actions were not influenced in the presence of heparin (200 U/ml). In endothelium-denuded strips, protamine (400ug/ml) inhibited Ca++ induced contraction, which was evoked in Ca++-free solution containing 40 mM K+, and also inhibited the norepinephrine (NE)-induced contraction. Protamine inhibited on the NE-induced contraction, but not the caffein-induced contration in Ca++ free, 2 mM EGTA solution. Also, such inhibition of contracions were not inluenced in the presence of heparin (40 U/ml).
CONCLUSION
This study demonstrates that protamine (in the presence or absence of heparin) acts on endothelial cell receptors to stimulate the production of nitric oxide and inhibits both Ca++-influx and the NE-induced Ca++ release from intracellular stores.
Key Words: Animals, rats; Arteries, aorta; Blood, anticoagulants, heparin, protamine; Blood vessels, vasodiataion
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