Glomerular injury induced by hydrogen peroxide: modifying influence of ACE inhibitors.
The sensitivity of isolated glomeruli from normotensive (Wistar-Kyoto, WKY) and spontaneously hypertensive (SHR) strains to oxidant stress was studied by determining the incidence of pyknosis, karyohexis and karyolysis after incubation with different concentrations of hydrogen peroxide (H2O2) (4.7 x 10(-9) - 10(-3) M). Even though the proportion of glomeruli containing nuclei that demonstrated these features increased progressively with increasing concentrations of H2O2, the number of severely damaged glomeruli was relatively small even at concentrations of 4.7 x 10(-3) M. Examination of the surface epithelial cells of glomeruli using scanning electron microscopy revealed no evidence of disturbance of the macroscopic or podocyte structure or, of increased blebbing after H2O2-treatment. These data suggest damage to nuclei is an early result of ROS stress on glomeruli. Preincubation of WKY glomeruli with captopril or lisinopril resulted in a significant drop in the proportion of WKY glomeruli demonstrating structural damage after oxidant stress. In contrast, preincubation of SHR glomeruli with lisinopril had no effect on oxidant-induced changes in the morphology of SHR glomeruli, whereas captopril effected a significant increase in the proportion of glomeruli demonstrating damage at all concentration of H2O2.
Clayton
L
L
Renal Laboratory School of Postgraduate Medicine, Keele University, North Staffordshire Hospital Centre, Stoke-on-Trent, UK.
Hiley
C
C
Davies
S
S
D'Souza
R
R
Jones
P
P
Strange
R
R
Aber
G
G
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors*; D006973:Hypertension / Q000503:physiopathology*; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D008297:Male; D008855:Microscopy, Electron, Scanning; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide