The Epoxyeicosatrienoic Acid Analog, PVPA, Ameliorates Cyclosporine-Induced Hypertension and Renal Injury in Rats.

The Epoxyeicosatrienoic Acid Analog, PVPA, Ameliorates Cyclosporine-Induced Hypertension and Renal Injury in Rats. Am J Physiol Renal Physiol. 2016 Jun 29;:ajprenal.00288.2016 Authors: Yeboah MM, Khan MA, Chesnik MA, Sharma A, Paudyal MP, Falck JR, Imig JD Abstract The introduction of calcineurin inhibitors (CNI) into clinical practice in the late 1970s transformed organ transplantation and led to significant improvement in acute rejection episodes. However, despite their significant clinical utility, the use of these agents is hampered by the development of hypertension and nephrotoxicity, which ultimately lead to end-stage kidney disease and overt cardiovascular outcomes. There are currently no effective agents to treat or prevent these complications. Importantly, CNI-free immunosuppressive regimens lack the overall efficacy of CNI-based treatments and put patients at risk of allograft rejection. Cytochrome P-450 epoxygenase metabolites of arachidonic acid, epoxyeicosatrienoic acids (EETs) have potent vasodilator and anti-hypertensive properties in addition to many cytoprotective effects, but their effects on CNI-induced nephrotoxicity have not been explored. Here, we show that PVPA, a novel orally active analog of 14,15-epoxyeicosatrienoic acid, effectively prevents the development of hypertension and ameliorates kidney injury in cyclosporine-treated rats. PVPA treatment reduced proteinuria and renal dysfunction induced by cyclosp...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research