American journal of physiology. Regulatory, integrative and comparative physiology, 2008-12, Vol.295 (6), p.R1858-R1865
2008
Details
- Autor(en) / Beteiligte
- Titel
- NADPH oxidase contributes to renal damage and dysfunction in Dahl salt-sensitive hypertension
- Ist Teil von
- American journal of physiology. Regulatory, integrative and comparative physiology, 2008-12, Vol.295 (6), p.R1858-R1865
- Ort / Verlag
- United States: American Physiological Society
- Erscheinungsjahr
- 2008
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi Submitted 31 July 2008 ; accepted in final form 13 October 2008 The goal of this study was to test the hypothesis that NADPH oxidase contributes importantly to renal cortical oxidative stress and inflammation, as well as renal damage and dysfunction, and increases in arterial pressure. Fifty-four 7- to 8-wk-old Dahl salt-sensitive (S) or R/Rapp strain rats were maintained for 5 wk on a high sodium (8%) or high sodium + apocynin (1.5 mmol/l in drinking water). Arterial and venous catheters were implanted on day 21 . By day 35 in the high-Na S rats, mRNA expression of renal cortical gp91phox, p22phox, p47phox, and p67phox NADPH subunits in S rats increased markedly, and treatment of high-Na S rats with the NADPH oxidase inhibitor apocynin resulted in significant decreases in mRNA expression of these NADPH oxidase subunits. At the same time, in apocynin-treated S rats 1 ) renal cortical GSH/GSSG ratio increased, 2 ) renal cortical O 2 – release and NADPH oxidase activity decreased, and 3 ) renal glomerular and interstitial damage markedly fell. Apocynin also decreased renal cortical monocyte/macrophage infiltration, and apocynin, but not the xanthine oxidase inhibitor allopurinol, attenuated decreases in renal hemodynamics and lowered arterial pressure. These data suggest that NADPH oxidase plays an important role in causing renal cortical oxidative stress and inflammation, which lead to decreases in renal hemodynamics, renal cortical damage, and increases in arterial pressure. renal failure; apocynin; renal hemodynamics; oxidative stress; inflammation Address for reprint requests and other correspondence: R. Davis Manning, Jr., Dept. of Physiology and Biophysics, 2500 N. State St., Jackson, MS 39216
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0363-6119eISSN: 1522-1490DOI: 10.1152/ajpregu.90650.2008Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2685289
- Format
- –
- Schlagworte
- Acetophenones - pharmacology, Allopurinol - pharmacology, Animals, Blood Pressure, Disease Models, Animal, Enzyme Inhibitors - pharmacology, Gene expression, Gene Expression Regulation, Enzymologic, Glomerular Filtration Rate, Glutathione - metabolism, Glutathione Disulfide - metabolism, Heart Rate, Hemodynamics - drug effects, Hemodynamics and Cardiorenal Integration, Hypertension, Hypertension - complications, Hypertension - enzymology, Hypertension - etiology, Hypertension - pathology, Hypertension - physiopathology, Inflammation - enzymology, Inflammation - physiopathology, Kidney Cortex - drug effects, Kidney Cortex - enzymology, Kidney Cortex - pathology, Kidney Cortex - physiopathology, Kidney diseases, Kidney Diseases - enzymology, Kidney Diseases - etiology, Kidney Diseases - pathology, Kidney Diseases - physiopathology, Kidneys, Macrophages - metabolism, Monocytes - metabolism, NADPH Oxidases - antagonists & inhibitors, NADPH Oxidases - genetics, NADPH Oxidases - metabolism, Oxidative Stress - drug effects, Protein Subunits, Proteinuria - enzymology, Proteinuria - physiopathology, Rats, Rats, Inbred Dahl, Renal Circulation, RNA, Messenger - metabolism, Rodents, Sodium Chloride, Dietary, Studies, Superoxides - metabolism, Time Factors, Xanthine Oxidase - antagonists & inhibitors, Xanthine Oxidase - metabolism