Document Detail

Protamine sulfate causes endothelium-independent vasorelaxation via inducible nitric oxide synthase pathway.
MedLine Citation:
PMID:  16434757     Owner:  NLM     Status:  MEDLINE    
PURPOSE: The precise mechanism of systemic hypotension frequently observed with the use of protamine is unclear. Although it has been reported that protamine stimulates the release of nitric oxide (NO) from endothelium NO synthase (eNOS), the association with inducible NOS (iNOS) remains unknown, despite the induction of iNOS by lipopolysaccharides (LPS) and/or inflammatory cytokines during cardiopulmonary bypass (CPB). The purpose of this study was to determine whether protamine stimulates the release of NO from iNOS induced by LPS. METHODS: We performed prospective and controlled functional examinations with isolated endothelium-denuded thoracic aortas from 21 male Wister rats. Aortic strips were mounted in Krebs solution and treated with LPS (1 microg x mL(-1)) for six hours to induce iNOS. Changes in tension caused by L-arginine (a substrate of NOS), protamine or a heparin-protamine complex (heparin: protamine = 1 unit: 10 microg) were measured in strips pre-contracted by phenylephrine. RESULTS: No drug relaxed the strips before LPS-treatment, but each drug relaxed the strips in a dose-dependent manner after LPS-treatment (P < 0.05). Aminoguanidine (an iNOS inhibitor) and methylene blue (a guanylyl cyclase inhibitor) inhibited the relaxations. CONCLUSION: These results indicate that protamine and the heparin-protamine complex stimulated the release of NO from iNOS. As iNOS is induced during CPB, protamine or a heparin-protamine complex might cause systemic hypotension, at least in part, by stimulating iNOS.
Ko Takakura; Maki Mizogami; Satoru Fukuda
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Canadian journal of anaesthesia = Journal canadien d'anesthésie     Volume:  53     ISSN:  0832-610X     ISO Abbreviation:  Can J Anaesth     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-01-25     Completed Date:  2006-06-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8701709     Medline TA:  Can J Anaesth     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  162-7     Citation Subset:  IM    
Department of Anesthesiology, Asahi University, 1851-1 Hozumi, Mizuho, Gifu 501-0296, Japan.
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MeSH Terms
Aorta, Thoracic
Arginine / pharmacology
Dose-Response Relationship, Drug
Endothelium, Vascular / metabolism,  physiology*
Enzyme Inhibitors / pharmacology
Guanidines / pharmacology
Heparin / pharmacology
Heparin Antagonists / pharmacology*
Lipopolysaccharides / pharmacology
Methylene Blue / pharmacology
Nitric Oxide / metabolism
Nitric Oxide Synthase Type II / antagonists & inhibitors,  metabolism*
Protamines / pharmacology*
Rats, Wistar
Vasodilation / drug effects*
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Guanidines; 0/Heparin Antagonists; 0/Lipopolysaccharides; 0/Protamines; 0/protamine heparin aggregate; 10102-43-9/Nitric Oxide; 61-73-4/Methylene Blue; 74-79-3/Arginine; 79-17-4/pimagedine; 9005-49-6/Heparin; EC Oxide Synthase Type II

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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