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Analysis Of Agonist‐Evoked Nitric Oxide Release From Human Endothelial Cells: Role Of Superoxide Anion
Author(s) -
DavidDufilho Monique,
Brunet Annie,
Privat Christelle,
Devynck MarieAude
Publication year - 2001
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2001.03565.x
Subject(s) - superoxide , nitric oxide , chemistry , agonist , extracellular , biochemistry , nitric oxide synthase , nicotinamide adenine dinucleotide phosphate , arginine , superoxide dismutase , endothelium , biophysics , pharmacology , receptor , endocrinology , oxidase test , biology , enzyme , organic chemistry , amino acid
SUMMARY 1. Dichlorofluorescein oxidation and electrochemical monitoring of in situ nitric oxide (NO) release from cultured human endothelial cells reveals that agonists such as thrombin and histamine simultaneously stimulate transient superoxide production. 2. The duration of ·NO release was increased only in the simultaneous presence of extracellular L ‐arginine and exogenous superoxide dismutase. In contrast, the inhibition of membrane reduced nicotinamide adenine dinucleotide (phosphate) oxidases, the major source of ·O 2 – in endothelial cells, did not prolong ·NO release, although extracellular L ‐arginine was also present. Comparison of these two experimental conditions suggested that H 2 O 2 was involved in the extension of the ·NO signal. 3. The present study demonstrates that, in the absence of external L ‐arginine, ·O 2 – production does not constitute the major pathway controlling the duration of agonist‐induced ·NO signal. These results suggest that L ‐arginine and H 2 O 2 act jointly to maintain nitric oxide synthase in an activated form.