Adrenalectomy prevents renal ischemia-reperfusion injury.
Spironolactone treatment prevents renal damage induced by ischemia-reperfusion (I/R), suggesting that renoprotection conferred by spironolactone is mediated by mineralocorticoid receptor (MR) blockade. It is possible, however, that this effect is due to other mechanisms. Therefore, this study evaluated whether adrenalectomy prevented renal damage induced by I/R. Three groups of Wistar rats were studied: 1) a group subjected to a sham surgery, 2) a group subjected to bilateral I/R, and 3) a group of rats in which adrenal glands were removed 3 days before induction of I/R. As expected, I/R resulted in renal dysfunction and severe tubular injury that was associated with a significant increase in tubular damage markers. In contrast, there was no renal dysfunction or tubular injury in rats that were adrenalectomized before I/R. These effects were demonstrated by normalization of glomerular filtration rate, markers of oxidative stress, and tubular injury markers in adrenalectomized rats. The renoprotection observed was associated with the reestablishment of nitric oxide metabolites, increased endothelial nitric oxide synthase expression and its activating phosphorylation, as well as normalization of Rho-kinase expression and ET(A) mRNA levels. Our results show that aldosterone plays a central role in the pathogenesis of renal damage induced by I/R and that MR blockade may be a promising strategy that opens a new therapeutic option for preventing acute renal injury.
Ramírez
Victoria
V
Unidad de Fisiología Molecular, Vasco de Quiroga No. 15, Tlalpan, 14000 México City, Mexico.
Trujillo
Joyce
J
Valdes
Rafael
R
Uribe
Norma
N
Cruz
Cristino
C
Gamba
Gerardo
G
Bobadilla
Norma A
NA
D000315:Adrenalectomy; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D007668:Kidney / Q000293:injuries* / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013148:Spironolactone; D054460:rho-Associated Kinases / Q000378:metabolism
D044022:Receptor, Endothelin A; D013148:Spironolactone; D009569:Nitric Oxide; D000450:Aldosterone; D052250:Nitric Oxide Synthase Type III; D054460:rho-Associated Kinases