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Diabetes‐induced NOS1 and NOS2 activity blunts oxygen consumption in renal medullary thick ascending limbs
Author(s) -
Foster Jan M.,
Carmines Pamela K.,
Pollock Jennifer S.
Publication year - 2010
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.24.1_supplement.812.10
Subject(s) - apocynin , superoxide , endocrinology , medicine , chemistry , ouabain , nadph oxidase , stimulation , reactive oxygen species , biochemistry , sodium , biology , organic chemistry , enzyme
We recently reported that diabetes increases superoxide anion and NO production by the rat renal medullary thick ascending limb (mTAL). We hypothesized that endogenously‐produced NO and superoxide anion exert opposing effects on Na transport by the mTAL during diabetes. O 2 consumption (Q O 2 ) by mTAL suspensions was measured using the BD ™ Oxygen Biosensor System, which discloses Q O 2 as a time‐related increase in relative fluorescence units (ΔRFU/min/mg protein). Ouabain‐sensitive Q O 2 (a measure of active Na + transport) averaged 0.08±0.02 in mTALs from sham rats and 0.22±0.04 in mTALs from rats with STZ‐induced diabetes ( P <0.05; n=8–9). NOS inhibition (100 μM 1400W) did not alter ouabain‐sensitive Q O 2 by mTALs from sham or STZ rats. NADPH oxidase inhibition (100 μM apocynin) had no effect on Q O 2 by sham mTALs, but caused a 60% decrease in ouabain‐sensitive Q O 2 by STZ mTALs ( P <0.05). In the presence of apocynin, NOS inhibition significantly increased ouabain‐sensitive Q O 2 by mTALs from STZ rats, with similar effects evoked by isoform‐specific inhibitors of NOS1 and NOS2 (1 μM VNIO and 100 nM 1400W, respectively). Thus, while neither NO nor superoxide anion tonically influences Na transport by mTALs from the normal rat kidney, diabetes triggers superoxide anion stimulation of Na transport that is attenuated by NOS1‐ and NOS2‐dependent mechanisms likely reflecting an inhibitory influence of NO. (Supported by the AHA)