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Soluble Guanylate Cyclase Catalyzes Nitrite reduction to Nitric Oxide in Rat Aortic Smooth Muscle Cells
Author(s) -
Madrasi Kumpal,
Tsoukias Nikolaos,
Joshi Mahesh
Publication year - 2011
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.25.1_supplement.643.17
Subject(s) - gucy1a3 , nitric oxide , nitrite , gucy1b3 , guanylate cyclase , chemistry , smooth muscle , biochemistry , medicine , guanylate cyclase 2c , nitrate , organic chemistry
Nitrite (NO2‐), although considered biologically inert, has been recently shown to be an important source of Nitric Oxide (NO) especially in hypoxic conditions. However, the mechanism through which it produces NO is not clearly understood. A wide range of mediators have been proposed including xanthine oxidoreductase, and heme proteins like myoglobin and hemoglobin. Here we have investigated the hypothesis that the soluble guanylate cyclase (sGC) in vascular smooth muscle cells catalyzes the reduction of NO2‐ to NO. Cultured A7r5 aortic smooth muscle cells (0.2×106 cells/35 mm dish) were loaded with an NO specific copper based trappable fluorescein dye [Cu2(FL2E)] and fluorescence measured with Olympus IX 81 microscope after addition of 30–60 mM NO2‐. There was several fold increase in NO synthesis which could be completely inhibited by ODQ (10 μM), a sGC inhibitor. However, there was no measurable NO synthesis at lower [NO2‐]. These data demonstrate that sGC in smooth muscle cells mediates the reduction of NO2‐ to NO under normoxic conditions. Thus NO2‐ may serve as an additional NO source in the vasculature complementary to nitric oxide synthase‐dependent NO release.