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This Article Full Text Full Text (PDF) All Versions of this Article: 297/4/F932    most recent 00252.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ramírez, V. Articles by Bobadilla, N. A. PubMed PubMed Citation Articles by Ramírez, V. Articles by Bobadilla, N. A.

Adrenalectomy prevents renal ischemia-reperfusion injury

¹Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, and ; Departments of ²Nephrology, ; ³Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, and Instituto Nacional de Cardiología Ignacio Chávez Mexico City Mexico

Submitted May 6, 2009 ; accepted in final form August 3, 2009

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.

endothelin; mineralocorticoid receptor; oxidative stress; Rho-kinase