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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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2017
760.pdf (720.5Kb)
Authors
Karanović, Danijela
Grujić-Milanović, Jelica
Miloradović, Zoran
Ivanov, Milan
Jovović, Đurđica
Vajić, Una-Jovana
Ćirović, Sanja
Marković-Lipkovski, Jasmina
Mihailović-Stanojević, Nevena
Article (Published version)
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Abstract
Down-regulation of nitric oxide synthase (NOS) and NO defi ciency 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 signifi cantly 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 signifi cant... decline in the glomerular fi ltration 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 fi broblasts and myofi broblasts 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.

Keywords:
adriamycin nephropathy / hypertension / nitric oxide synthase / losartan / tempol
Source:
Acta Veterinaria-Beograd, 2017, 67, 3, 409-425
Publisher:
  • Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd
Funding / projects:
  • Investigation of antihypertensiv? and renoprotectiv? potential of natural and synthetic compounds in the experimental models of cardiovascular and renal diseases (RS-175096)

DOI: 10.1515/acve-2017-0033

ISSN: 0567-8315

WoS: 000413331900009

Scopus: 2-s2.0-85030720983
[ Google Scholar ]
2
2
URI
http://rimi.imi.bg.ac.rs/handle/123456789/763
Collections
  • Radovi istraživača / Researchers' publications
Institution/Community
Institut za medicinska istraživanja
TY  - JOUR
AU  - Karanović, Danijela
AU  - Grujić-Milanović, Jelica
AU  - Miloradović, Zoran
AU  - Ivanov, Milan
AU  - Jovović, Đurđica
AU  - Vajić, Una-Jovana
AU  - Ćirović, Sanja
AU  - Marković-Lipkovski, Jasmina
AU  - Mihailović-Stanojević, Nevena
PY  - 2017
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/763
AB  - Down-regulation of nitric oxide synthase (NOS) and NO defi ciency 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 signifi cantly 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 signifi cant decline in the glomerular fi ltration 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 fi broblasts and myofi broblasts 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.
PB  - Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd
T2  - Acta Veterinaria-Beograd
T1  - Effects of losartan, tempol, and their combination on renal nitric oxide synthases in the animal model of chronic kidney disease
EP  - 425
IS  - 3
SP  - 409
VL  - 67
DO  - 10.1515/acve-2017-0033
ER  - 
@article{
author = "Karanović, Danijela and Grujić-Milanović, Jelica and Miloradović, Zoran and Ivanov, Milan and Jovović, Đurđica and Vajić, Una-Jovana and Ćirović, Sanja and Marković-Lipkovski, Jasmina and Mihailović-Stanojević, Nevena",
year = "2017",
abstract = "Down-regulation of nitric oxide synthase (NOS) and NO defi ciency 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 signifi cantly 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 signifi cant decline in the glomerular fi ltration 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 fi broblasts and myofi broblasts 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.",
publisher = "Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd",
journal = "Acta Veterinaria-Beograd",
title = "Effects of losartan, tempol, and their combination on renal nitric oxide synthases in the animal model of chronic kidney disease",
pages = "425-409",
number = "3",
volume = "67",
doi = "10.1515/acve-2017-0033"
}
Karanović, D., Grujić-Milanović, J., Miloradović, Z., Ivanov, M., Jovović, Đ., Vajić, U., Ćirović, S., Marković-Lipkovski, J.,& Mihailović-Stanojević, N.. (2017). Effects of losartan, tempol, and their combination on renal nitric oxide synthases in the animal model of chronic kidney disease. in Acta Veterinaria-Beograd
Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd., 67(3), 409-425.
https://doi.org/10.1515/acve-2017-0033
conv_4150
Karanović D, Grujić-Milanović J, Miloradović Z, Ivanov M, Jovović Đ, Vajić U, Ćirović S, Marković-Lipkovski J, Mihailović-Stanojević N. Effects of losartan, tempol, and their combination on renal nitric oxide synthases in the animal model of chronic kidney disease. in Acta Veterinaria-Beograd. 2017;67(3):409-425.
doi:10.1515/acve-2017-0033
conv_4150 .
Karanović, Danijela, Grujić-Milanović, Jelica, Miloradović, Zoran, Ivanov, Milan, Jovović, Đurđica, Vajić, Una-Jovana, Ćirović, Sanja, Marković-Lipkovski, Jasmina, Mihailović-Stanojević, Nevena, "Effects of losartan, tempol, and their combination on renal nitric oxide synthases in the animal model of chronic kidney disease" in Acta Veterinaria-Beograd, 67, no. 3 (2017):409-425,
https://doi.org/10.1515/acve-2017-0033 .,
conv_4150 .

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