Key result
Preincubation with captopril or lisinopril reduced oxidant-induced structural damage in WKY glomeruli, but in SHR glomeruli lisinopril had no effect and captopril increased damage.
Why the study?
Does preincubation with captopril or lisinopril modify hydrogen peroxide-induced structural damage in isolated glomeruli from normotensive and hypertensive rats?
Does preincubation with captopril or lisinopril modify hydrogen peroxide-induced structural damage in isolated glomeruli from normotensive and hypertensive rats?
ACE inhibitors exhibit differential, strain-dependent effects on oxidant-induced glomerular injury, with captopril paradoxically exacerbating damage in glomeruli from spontaneously hypertensive rats.
Answers are grounded in this paper and cite their sources.
Rat strain-specific ACEI effects on glomerular oxidant injury do not inform clinical practice; leaves open targeted human research.
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.
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Clayton et al. (1992) studied Glomerular injury induced by oxidant stress. Hydrogen peroxide (H2O2) with or without captopril or lisinopril preincubation vs. No preincubation / different strains was evaluated on Incidence of pyknosis, karyohexis and karyolysis (structural damage). Preincubation with captopril or lisinopril reduced oxidant-induced structural damage in WKY glomeruli, but in SHR glomeruli lisinopril had no effect and captopril increased damage.
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