Activated intrarenal reactive oxygen species and renin angiotensin system in IgA nephropathy.
Immunoglobulin A (IgA) nephropathy is recognized worldwide as the most common primary glomerulopathy. Although the mechanisms underlying the development of IgA nephropathy are gradually being clarified, their details remain unclear, and a radical cure for this condition has not yet been established. It has been clinically demonstrated that the immunoreactivities of intrarenal heme oxygenase-1 (HO-1) and 4-hydroxy-2-nonenal (4-HNE) markers of reactive oxygen species (ROS) and those of intrarenal angiotensinogen (AGT) and angiotensin II (Ang II) markers of renin angiotensin system (RAS) in IgA nephropathy patients were significantly increased as compared to those of control subjects. In an animal study, high IgA of ddY (HIGA) mice were used as an IgA nephropathy model and compared with BALB/c mice, which served as the control. The levels of markers for ROS (urinary 8-isoprostane and intrarenal 4-HNE), RAS (intrarenal AGT and Ang II), and renal damage in the HIGA mice were significantly increased as compared to those in the BALB/c mice. Moreover, an interventional study using HIGA mice demonstrated that the expressions of 2 lines of intrarenal ROS markers (4-HNE and HO-1), 2 lines of intrarenal RAS markers (AGT and Ang II) and renal damage decreased significantly in HIGA mice receiving treatment with the Ang II receptor blocker olmesartan but not in HIGA mice receiving treatment with RAS-independent antihypertensive drugs (hydralazine, reserpine, and hydrochlorothiazide) when compared with HIGA mice that were not treated. These data suggest that intrarenal ROS and RAS activation plays a pivotal role in the development of IgA nephropathy.
Department of Physiology, and Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, LA 70112-2699, USA.
N
N
Ohashi
M
M
Urushihara
H
H
Kobori
D000447:Aldehydes / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000808:Angiotensinogen / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D019317:Evidence-Based Medicine; D005922:Glomerulonephritis, IGA / Q000378:metabolism* / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012084:Renin-Angiotensin System; D014662:Vasoconstrictor Agents / Q000378:metabolism
D000447:Aldehydes; D015415:Biomarkers; D015853:Cysteine Proteinase Inhibitors; D017382:Reactive Oxygen Species; D014662:Vasoconstrictor Agents; D000808:Angiotensinogen; D000804:Angiotensin II; D051547:Heme Oxygenase-1; C027576:4-hydroxy-2-nonenal