Packed red blood cells are an abundant and proximate potential source of nitric oxide synthase inhibition

PloS One
Charles F ZwemerLouis G D'Alecy

Abstract

We determined, for packed red blood cells (PRBC) and fresh frozen plasma, the maximum content, and ability to release the endogenous nitric oxide synthase (NOS) inhibitors asymmetric dimethylarginine (ADMA) and monomethylarginine (LNMMA). ADMA and LNMMA are near equipotent NOS inhibitors forming blood's total NOS inhibitory content. The balance between removal from, and addition to plasma determines their free concentrations. Removal from plasma is by well-characterized specific hydrolases while formation is restricted to posttranslational protein methylation. When released into plasma they can readily enter endothelial cells and inhibit NOS. Fresh rat and human whole blood contain substantial protein incorporated ADMA however; the maximum content of ADMA and LNMMA in PRBC and fresh frozen plasma has not been determined. We measured total (free and protein incorporated) ADMA and LNMMA content in PRBCs and fresh frozen plasma, as well as their incubation induced release, using HPLC with fluorescence detection. We tested the hypothesis that PRBC and fresh frozen plasma contain substantial inhibitory methylarginines that can be released chemically by complete in vitro acid hydrolysis or physiologically at 37°C by enzymatic blood p...Continue Reading

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Citations

Jun 28, 2016·Scientific Reports·Shunmugan NagarajanSuvro Chatterjee
Aug 25, 2017·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Kenneth R OlsonKarl D Straub
Aug 9, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Joanne F GarbinciusDaniel E Michele
Jun 3, 2021·International Journal of Molecular Sciences·Jakub MocholAdrian Doroszko

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Methods Mentioned

BETA
Protein Assay
size exclusion chromatography
blood draw

Software Mentioned

ChemDraw

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