Effects of Losartan, Tempol, and Their Combination On Renal Nitric Oxide Synthases in the Animal Model of Chronic Kidney Disease

Down-regulation of nitric oxide synthase (NOS) and NO deficiency in the kidneys have been implicated in the pathogenesis of chronic kidney disease (CKD). In this study we examined the effects of losartan, tempol, and combined treatment on three NOS isoforms expressions, kidney NO content and NOS cor...

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Autores principales:	Karanovic Danijela, Grujic-Milanovic Jelica, Miloradovic Zoran, Ivanov Milan, Jovovic Djurdjica, Vajic Una-Jovana, Cirovic Sanja, Markovic-Lipkovski Jasmina, Mihailovic-Stanojevic Nevena
Formato:	article
Lenguaje:	EN
Publicado:	Sciendo 2017
Materias:	adriamycin nephropathy hypertension nitric oxide synthase losartan tempol Veterinary medicine SF600-1100
Acceso en línea:	https://doaj.org/article/f0330bb131344c36a370aa8446703eb8
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spelling	oai:doaj.org-article:f0330bb131344c36a370aa8446703eb82021-11-17T21:27:51ZEffects of Losartan, Tempol, and Their Combination On Renal Nitric Oxide Synthases in the Animal Model of Chronic Kidney Disease1820-744810.1515/acve-2017-0033https://doaj.org/article/f0330bb131344c36a370aa8446703eb82017-09-01T00:00:00Zhttps://doi.org/10.1515/acve-2017-0033https://doaj.org/toc/1820-7448Down-regulation of nitric oxide synthase (NOS) and NO deficiency in the kidneys have been implicated in the pathogenesis of chronic kidney disease (CKD). In this study we examined the effects of losartan, tempol, and combined treatment on three NOS isoforms expressions, kidney NO content and NOS correlation with renal function and structure in the early stage of adriamycin (ADR)-induced CKD in spontaneously hypertensive rats (SHR). Rats were divided into control group, and four other groups which were treated with ADR and received vehicle, losartan (L, angiotensin II type 1 receptor blocker), tempol (T, redox-cycling nitroxide) or T+L treatment (by gavage) in a six-week study. Reduction of all NOS isoforms expressions were significantly improved by losartan or tempol, and correlated with proteinuria amelioration. Combined treatment induced down-regulation of constitutive NOS isoforms, whilst inducible NOS was up-regulated and followed by increased nitrite content and a significant decline in the glomerular filtration rate. Losartan or tempol prevented ADR-induced neoexpression of vimentin in the glomeruli and tubulointerstital areas, whereas de novo vimentin expression was still observed in the atrophic tubules and in the interstitial fibroblasts and myofibroblasts in combined treatment. It can be concluded that single treatments, contrary to combined, were effective in improving NO bioavailability and slowing down the progression of CKD.Karanovic DanijelaGrujic-Milanovic JelicaMiloradovic ZoranIvanov MilanJovovic DjurdjicaVajic Una-JovanaCirovic SanjaMarkovic-Lipkovski JasminaMihailovic-Stanojevic NevenaSciendoarticleadriamycin nephropathyhypertensionnitric oxide synthaselosartantempolVeterinary medicineSF600-1100ENActa Veterinaria, Vol 67, Iss 3, Pp 409-425 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	adriamycin nephropathy hypertension nitric oxide synthase losartan tempol Veterinary medicine SF600-1100
spellingShingle	adriamycin nephropathy hypertension nitric oxide synthase losartan tempol Veterinary medicine SF600-1100 Karanovic Danijela Grujic-Milanovic Jelica Miloradovic Zoran Ivanov Milan Jovovic Djurdjica Vajic Una-Jovana Cirovic Sanja Markovic-Lipkovski Jasmina Mihailovic-Stanojevic Nevena Effects of Losartan, Tempol, and Their Combination On Renal Nitric Oxide Synthases in the Animal Model of Chronic Kidney Disease
description	Down-regulation of nitric oxide synthase (NOS) and NO deficiency in the kidneys have been implicated in the pathogenesis of chronic kidney disease (CKD). In this study we examined the effects of losartan, tempol, and combined treatment on three NOS isoforms expressions, kidney NO content and NOS correlation with renal function and structure in the early stage of adriamycin (ADR)-induced CKD in spontaneously hypertensive rats (SHR). Rats were divided into control group, and four other groups which were treated with ADR and received vehicle, losartan (L, angiotensin II type 1 receptor blocker), tempol (T, redox-cycling nitroxide) or T+L treatment (by gavage) in a six-week study. Reduction of all NOS isoforms expressions were significantly improved by losartan or tempol, and correlated with proteinuria amelioration. Combined treatment induced down-regulation of constitutive NOS isoforms, whilst inducible NOS was up-regulated and followed by increased nitrite content and a significant decline in the glomerular filtration rate. Losartan or tempol prevented ADR-induced neoexpression of vimentin in the glomeruli and tubulointerstital areas, whereas de novo vimentin expression was still observed in the atrophic tubules and in the interstitial fibroblasts and myofibroblasts in combined treatment. It can be concluded that single treatments, contrary to combined, were effective in improving NO bioavailability and slowing down the progression of CKD.
format	article
author	Karanovic Danijela Grujic-Milanovic Jelica Miloradovic Zoran Ivanov Milan Jovovic Djurdjica Vajic Una-Jovana Cirovic Sanja Markovic-Lipkovski Jasmina Mihailovic-Stanojevic Nevena
author_facet	Karanovic Danijela Grujic-Milanovic Jelica Miloradovic Zoran Ivanov Milan Jovovic Djurdjica Vajic Una-Jovana Cirovic Sanja Markovic-Lipkovski Jasmina Mihailovic-Stanojevic Nevena
author_sort	Karanovic Danijela
title	Effects of Losartan, Tempol, and Their Combination On Renal Nitric Oxide Synthases in the Animal Model of Chronic Kidney Disease
title_short	Effects of Losartan, Tempol, and Their Combination On Renal Nitric Oxide Synthases in the Animal Model of Chronic Kidney Disease
title_full	Effects of Losartan, Tempol, and Their Combination On Renal Nitric Oxide Synthases in the Animal Model of Chronic Kidney Disease
title_fullStr	Effects of Losartan, Tempol, and Their Combination On Renal Nitric Oxide Synthases in the Animal Model of Chronic Kidney Disease
title_full_unstemmed	Effects of Losartan, Tempol, and Their Combination On Renal Nitric Oxide Synthases in the Animal Model of Chronic Kidney Disease
title_sort	effects of losartan, tempol, and their combination on renal nitric oxide synthases in the animal model of chronic kidney disease
publisher	Sciendo
publishDate	2017
url	https://doaj.org/article/f0330bb131344c36a370aa8446703eb8
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Effects of Losartan, Tempol, and Their Combination On Renal Nitric Oxide Synthases in the Animal Model of Chronic Kidney Disease

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