Quinapril decreases renal endothelin-1 expression and synthesis in a normotensive model of immune-complex nephritis.

Journal of the American Society of Nephrology : JASN
Marta Ruiz-OrtegaJesús Egido

Abstract

Angiotensin-converting enzyme (ACE) inhibitors diminish proteinuria and the progression to renal failure in several experimental models of renal injury. Endothelin-1 (ET-1) possesses potent biological actions on renal vessels and has been considered as a potential mediator of renal damage. Because angiotensin II (Ang II) induces ET-1 synthesis in endothelial and mesangial cells, we hypothesized that some of the beneficial effects of the ACE inhibitors could result from the blockade of ET-1 synthesis. In a normotensive model of immune-complex nephritis, in which there exists an increase in renal ACE activity, the effect of the ACE inhibitor quinapril on preproET-1 and ETA receptor mRNA expression, as well as on ET-1 protein levels, was examined in this study. In relation to controls, nephritic rats showed an increase in preproET-1 and ETA receptor gene expression in renal cortex and medulla, coinciding with the maximal renal ACE activity. PreproET-1 mRNA (in situ hybridization) and ET-1 protein (immunohistochemistry) were localized in glomerular capillary walls, mesangial and glomerular epithelial cells, as well as in the brush border of some proximal tubules, and in small vessels. In nephritic rats, there was an increase in pre...Continue Reading

Citations

Feb 24, 2001·Current Opinion in Nephrology and Hypertension·A BenigniG Remuzzi
Oct 25, 2001·Journal of the American Society of Nephrology : JASN·Ingo LehrkeJürgen Wagner
May 8, 1999·Journal of the American Society of Nephrology : JASN·F RuschitzkaT F Lüscher
Jun 21, 2001·Hypertension Research : Official Journal of the Japanese Society of Hypertension·N KobayashiH Matsuoka
Jul 25, 2003·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Dorothea AppenrothChristian Fleck
Mar 17, 2006·Journal of the American Society of Nephrology : JASN·Neeraj DhaunDavid J Webb
Apr 4, 2007·Cardiovascular Drugs and Therapy·Jesus Egido, Marta Ruiz-Ortega
Mar 14, 2008·Journal of the American Society of Nephrology : JASN·Shunhua GuoCharles E Alpers
Sep 2, 2008·Canadian Journal of Physiology and Pharmacology·Jessica CaprioliAriela Benigni
Apr 2, 2009·European Journal of Clinical Investigation·L Longaretti, A Benigni

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