Regression of renal disease by angiotensin II antagonism is caused by regeneration of kidney vasculature

Andrea Remuzzi, Fabio Sangalli, Daniela MacConi, Susanna Tomasoni, Irene Cattaneo, Paola Rizzo, Barbara Bonandrini, Elena Bresciani, Lorena Longaretti, Elena Gagliardini, Sara Conti, Ariela Benigni, Giuseppe Remuzzi

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic renal insufficiency inexorably progresses in patients, such as it does after partial renal ablation in rats. However, the progression of renal diseases can be delayed by angiotensin II blockers that stabilize renal function or increaseGFR, even in advanced phases of the disease. Regression of glomerulosclerosis can be induced by angiotensin II antagonism, but the effect of these treatments on the entire vascular tree is unclear. Here, using microcomputed tomography and scanning electron microscopy,we compared the size and extension of kidney blood vessels in untreatedWistar rats with those in untreated and angiotensin II antagonist-treated MunichWistar Frömter (MWF) rats that spontaneously develop kidney disease with age. The kidney vasculature underwent progressive rarefaction in untreated MWF rats, substantially affecting intermediate and small vessels. Microarray analysis showed increased Tgf-b and endothelin-1 gene expression with age. Notably, 10-week inhibition of the renin-angiotensin system regenerated kidney vasculature and normalized Tgf-b and endothelin-1 gene expression in aged MWF rats. These changes were associated with reduced apoptosis, increased endothelial cell proliferation, and restoration of Nrf2 expression, suggesting mechanisms by which angiotensin II antagonism mediates regeneration of capillary segments. These results have important implications in the clinical setting of chronic renal insufficiency.

Original languageEnglish
Pages (from-to)699-705
Number of pages7
JournalJournal of the American Society of Nephrology
Volume27
Issue number3
DOIs
Publication statusPublished - Mar 1 2016

ASJC Scopus subject areas

  • Nephrology

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