| The Vasodilation of Protamine and the Influence of Heparin on its Actions in the Isolated Aortic Arteries of Rats. |
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Seok Hwa Yoon, Yoon Hee Kim, Sung Bum Kwon, Jung Eun Lee, Hai Ja Kim, Sae Jin Choi |
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| 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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