AT1R blockade with valsartan lowered systolic blood pressure by 30%, albuminuria by 91%, and kidney MDA by 80% in Ren2 rats compared with untreated controls.
Does valsartan reduce albuminuria and oxidative stress while improving glomerular filtration barrier integrity in Ren2 transgenic rats?
AT1R blockade with valsartan reduces blood pressure, albuminuria, and tissue oxidative stress while improving glomerular filtration barrier integrity in a transgenic rat model of hypertension.
TG(mRen2)27 (Ren2) transgenic rats overexpress the mouse renin gene, manifest hypertension, and exhibit increased tissue ANG II levels and oxidative stress. Evidence indicates that elevated tissue ANG II contributes to oxidative stress, increases in glomerular macromolecular permeability, and consequent albuminuria. Furthermore, angiotensin type 1 receptor (AT1R) blockers reduce albuminuria and slow progression of renal disease. However, it is not known whether improvements in glomerular filtration barrier integrity and albuminuria during treatment are related to reductions in oxidative stress and/or kidney renin-angiotensin system (RAS) activity. To investigate the renal protective effects of AT1R blockade, we treated young (6-7 wk old) male Ren2 rats with valsartan (Ren2-V; 30 mg/kg) for 3 wk and measured urine albumin, kidney malondialdehyde (MDA), RAS component mRNAs, and NADPH oxidase subunits (gp91(phox) and Rac1) compared with age-matched untreated Ren2 and Sprague-Dawley (S-D) rats. Basement membrane thickness, slit pore diameter and number, and foot process base width were measured by transmission electron microscopy (TEM). Results indicate that AT1R blockade lowered systolic blood pressure (30%), albuminuria (91%), and kidney MDA (80%) in Ren2-V compared with untreated Ren2 rats. Increased slit pore number and diameter and reductions in basement membrane thickness and podocyte foot process base width were strongly associated with albuminuria and significantly improved following AT1R blockade. AT1R blockade was also associated with increased angiotensin-converting enzyme-2 and neprilysin expression, demonstrating a beneficial shift in balance of renal RAS. Thus reductions in blood pressure, albuminuria, and tissue oxidative stress with AT1R blockade were associated with improved indexes of glomerular filtration barrier integrity and renal RAS in Ren2 rats.
Whaley‐Connell et al. (Wed,) conducted a other in Hypertension and glomerular filtration barrier injury. Valsartan vs. Untreated Ren2 and Sprague-Dawley rats was evaluated on Systolic blood pressure, albuminuria, and kidney malondialdehyde (MDA). AT1R blockade with valsartan lowered systolic blood pressure by 30%, albuminuria by 91%, and kidney MDA by 80% in Ren2 rats compared with untreated controls.