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Superoxide production in the medullary thick ascending limb modulates blood pressure
Author(s) -
Gongora Maria Carolina,
Lob Heinrich,
Blinder Yelena,
Harrison David G
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.792.5
Subject(s) - superoxide , medicine , endocrinology , angiotensin ii , nadph oxidase , sod1 , chemistry , renal medulla , kidney , oxidative stress , genetically modified mouse , afferent arterioles , superoxide dismutase , transgene , blood pressure , biology , biochemistry , gene , enzyme
Superoxide production in the renal medulla has been suggested to play a major role in modulating renal sodium and water handling and blood pressure control. To further study this, we created mice with loxP sites flanking the extracellular superoxide dismutase (SOD3) coding region and other mice with loxP sites flanking the NADPH oxidase subunit p22 phox . We also created transgenic mice with Cre driven by the Tamm Horsfall promoter (tg creth mice). SOD3 and the NADPH oxidase subunit p22 phox were then selectively deleted in the medullar thick ascending limb (mTAL) by crossing the phloxed SOD3 and p22 phox mice with tg creth mice. While baseline blood pressures were similar (114 +/−2.0 and 116 +/− 0.8 mmHg), the hypertensive response to two‐week infusion of angiotensin II (490 ng/kg/min) was markedly augmented in mice with deletion of mTAL SOD3 compared to controls (178 +/− 1.6 vs. 158 +/− 7.9, p = 0.007). In contrast, preliminary data show that mice with mTAL deletion p22 phox demonstrate a blunted hypertensive response to angiotensin II. We conclude that oxidative stress within the mTAL, as demonstrated in these unique genetically modified mice, critically regulates the hypertensive response to angiotensin II. Supported by AHA 09POST2100151 and NIH PPG PO1HL058000.