The Vasodilation of Protamine and the Influence of Heparin on its Actions in the Isolated Aortic Arteries of Rats.
10.4097/kjae.1997.33.4.591
- Author:
Seok Hwa YOON
;
Yoon Hee KIM
;
Sung Bum KWON
;
Jung Eun LEE
;
Hai Ja KIM
;
Sae Jin CHOI
- Publication Type:Original Article
- Keywords:
Animals, rats;
Arteries, aorta;
Blood, anticoagulants, heparin, protamine;
Blood vessels, vasodiataion
- MeSH:
Animals;
Arteries*;
Baths;
Cardiovascular System;
Egtazic Acid;
Endothelial Cells;
Endothelium;
Heparin*;
Hypotension;
Indomethacin;
Nitric Oxide;
Norepinephrine;
omega-N-Methylarginine;
Phenylephrine;
Rats*;
Relaxation;
Superoxide Dismutase;
Vasodilation*
- From:Korean Journal of Anesthesiology
1997;33(4):591-603
- CountryRepublic of Korea
- Language:Korean
-
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.
