Visualizing tubular lipid peroxidation in intact renal tissue in hypertensive rats.
An imbalance between production of reactive oxygen species (ROS) and antioxidant defense is involved in the pathogenesis of diverse chronic parenchymatous diseases. To identify the primary site of such increased oxidative stress, a lipophilic ROS-sensitive probe (C11-Bodipy 581/591) is introduced, which allows the visualization and quantification of oxidative injury using confocal fluorescence microscopy in living cells. The properties of this probe are such that its emission wavelength irreversibly shifts from red to green upon oxidation. This probe was used to identify the spatiotemporal distribution of lipid peroxidation in the rat kidney during chronic NOS inhibition, a model associated with hypertension and proteinuria. Chronic NOS inhibition resulted in increased lipid peroxidation in renal tubules but hardly any in glomeruli or blood vessels. This peroxidation preceded the loss of renal function characteristic of the model and was accompanied by parallel changes in thiobarbituric acid reactive substances in the renal cortex. Furthermore, the increase in oxidation was dependent on angiotensin II and NADPH oxidase and prevented by vitamin E. Induction of cytoprotective heat-shock protein 70 preceded lipid peroxidation, rise in BP, or proteinuria. These findings challenge the paradigm that the vascular wall is the source and target of oxidative stress in chronic parenchymatous renal disease associated with hypertension.
Bapat
Sujata
S
Department of Molecular Cell Biology, Institute of Biomembranes, Utrecht University Medical Center, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands.
Post
Jan Andries
JA
Braam
Branko
B
Goldschmeding
Roel
R
Koomans
Hein A
HA
Verkleij
Arie J
AJ
Joles
Jaap A
JA
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D015227:Lipid Peroxidation; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; D000804:Angiotensin II; D014810:Vitamin E; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D019255:NADPH Oxidases