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Endothelial Dysfunction in DOCA‐salt Hypertensive Mice: A Role for nNOS‐derived Hydrogen Peroxide
Author(s) -
Silva Grazielle,
Silva Josiane,
Diniz Thiago,
Lemos Virginia,
Cortes Steyner
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.623.3
Subject(s) - endothelial dysfunction , mesenteric arteries , vasodilation , medicine , endocrinology , myograph , enos , nitric oxide , chemistry , endothelium , western blot , acetylcholine , nitric oxide synthase , artery , biochemistry , gene
Aims investigated the involvement of neuronal nitric oxide synthase (nNOS) and H 2 O 2 in the impaired endothelium‐dependent vasodilatation of mesenteric arteries from DOCA‐salt hypertensive mice (DOCA‐salt). Methods and results Myograph studies were used to investigate the endothelium‐dependent vasodilator effect of acetylcholine (ACh), the protein expression by Western blot, H 2 O 2 formation by selective carbon microsensors permeable membrane and the protein localization in the endothelial layer of mesenteric arteries by immunofluorescence approved by ethics committee (protocol 227/08).The vasodilator effect of ACh is strongly impaired in mesenteric arteries from DOCA‐salt (SBP 180± 5 mmHg, Emax 51±2.3%) versus Sham (SBP 128±4 mmHg, Emax 99±1.2%). Nonselective inhibition of NOS strongly reduced the effect of ACh in both DOCA‐salt and Sham mice. Selective inhibition of nNOS and catalase induced a higher reduction in the effect of ACh in Sham than in DOCA‐salt. Production of H 2 O 2 induced by ACh was significantly smaller in vessels from DOCA‐salt and it was blunted after the inhibition of nNOS. The expression of both eNOS and nNOS were significantly smaller in DOCA‐salt, while the phosphorylation of their inhibitory site was increased. The presence of nNOS was confirmed in the endothelial layer of mesenteric arteries from both Sham and DOCA‐salt. Conclusion A reduction in nNOS‐derived H2O2 production in DOCA/salt hypertensive mice partially contributes to endothelial dysfunction. This opens a new perspective for the understanding of the endothelial dysfunction in hypertension. Financial support: CNPq