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Endothelin-A receptor blockade slows the progression of renal injury in experimental renovascular disease.
- Source :
- American Journal of Physiology: Renal Physiology; Jul2011, Vol. 301 Issue 1, pF218-F225, 8p
- Publication Year :
- 2011
-
Abstract
- Endothelin (ET)-1, a potent renal vasoconstrictor with mitogenic properties, is upregulated by ischemia and has been shown to induce renal injury via the ET-A receptor. The potential role of ET-A blockade in chronic renovascular disease (RVD) has not, to our knowledge, been previously reported. We hypothesized that chronic ET-A receptor blockade would preserve renal hemodynamics and slow the progression of injury of the stenotic kidney in experimental RVD. Renal artery stenosis, a major cause of chronic RVD, was induced in 14 pigs and observed for 6 wk. In half of the pigs, chronic ET-A blockade was initiated (RVD+ET-A, 0.75 mg∙kg<superscript>-1</superscript>∙day<superscript>-1</superscript>) at the onset of RVD. Single-kidney renal blood flow, glomerular filtration rate, and perfusion were quantified in vivo after 6 wk using multidetector computer tomography. Renal microvascular density was quantified ex vivo using three-dimensional microcomputer tomography, and growth factors, inflammation, apoptosis, and fibrosis were determined in renal tissue. The degree of stenosis and increase in blood pressure were similar in RVD and RVD+ET-A pigs. Renal hemodynamics, function, and microvascular density were decreased in the stenotic kidney but preserved by ET-A blockade, accompanied by increased renal expression of vascular endothelial growth factor, hepatocyte growth factor, and downstream mediators such as phosphorilated-Akt, angiopoietins, and endothelial nitric oxide synthase. ET-A blockade also reduced renal apoptosis, inflammation, and glomerulosclerosis. This study shows that ET-A blockade slows the progression of renal injury in experimental RVD and preserves renal hemodynamics, function, and microvascular density in the stenotic kidney. These results support a role for ET-1/ET-A as a potential therapeutic target in chronic RVD. [ABSTRACT FROM AUTHOR]
- Subjects :
- KIDNEY diseases
BLOOD circulation
CYTOKINES
ENDOTHELINS
HEMODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 1931857X
- Volume :
- 301
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- American Journal of Physiology: Renal Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 64394964
- Full Text :
- https://doi.org/10.1152/ajprenal.00089.2011