NADPH and heme redox modulate pulmonary artery relaxation and guanylate cyclase activation by NO
Department of Physiology, New York Medical College, Valhalla, New York 10595 The hemoprotein oxidant ferricyanide (FeCN) converts the iron of the heme on soluble guanylate cyclase (sGC) from Fe 2+ to Fe 3+ , which prevents nitric oxide (NO) from binding the heme and stimulating sGC activity. This st...
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Published in | American journal of physiology. Lung cellular and molecular physiology Vol. 277; no. 6; pp. 1124 - L1132 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.12.1999
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Subjects | |
Online Access | Get full text |
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Summary: | Department of Physiology, New York Medical College, Valhalla, New
York 10595
The hemoprotein oxidant ferricyanide (FeCN)
converts the iron of the heme on soluble guanylate cyclase (sGC) from
Fe 2+ to
Fe 3+ , which prevents nitric oxide
(NO) from binding the heme and stimulating sGC activity. This study
uses FeCN to examine whether modulation of the redox status of the heme
on sGC influences the relaxation of endothelium-removed bovine
pulmonary arteries (BPA) to NO. Pretreatment of the homogenate of BPA
with 50 µM FeCN resulted in a loss of stimulation of sGC activity by
the NO donor 10 µM S -nitroso- N -acetylpenicillamine
(SNAP). In the FeCN-treated homogenate reconcentrated to the enzyme
levels in BPA, 100 µM NADPH restored NO stimulation of sGC, and this
effect of NADPH was prevented by an inhibitor of flavoprotein electron
transport, 1 µM diphenyliodonium (DPI). In BPA the relaxation to SNAP
was not altered by FeCN, inhibitors of NADPH generation by the pentose
phosphate pathway [250 µM 6-aminonicotinamide (6-AN) and 100 µM epiandrosterone (Epi)], or 1 µM DPI. However, the
combination of FeCN with 6-AN, Epi, or DPI inhibited
( P < 0.05) relaxation to SNAP
without significantly altering the relaxation of BPA to forskolin. The
inhibitory effects of 1 µM
1 H -[1,2,4]oxadiazolo[4,3- a ]quinoxalin-1-one
(a probe that appears to convert NO-heme of sGC to its
Fe 3+ -heme form) on relaxation to
SNAP were also enhanced by DPI. These observations suggest that a
flavoprotein containing NADPH oxidoreductase may influence
cGMP-mediated relaxation of BPA to NO by maintaining the heme of sGC in
its Fe 2+ oxidation state.
NADPH oxidoreductase; nitric oxide; pentose phosphate pathway |
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ISSN: | 1040-0605 0002-9513 1522-1504 |
DOI: | 10.1152/ajplung.1999.277.6.l1124 |