Hyperhomocysteinemia-Induced Oxidative Stress Aggravates Renal Damage in Hypertensive Rats.
Albuminuria
Animals
Blood Pressure
Creatinine
/ urine
Glomerular Filtration Rate
Homocysteine
/ metabolism
Hyperhomocysteinemia
/ genetics
Hypertension
/ genetics
Kidney
/ metabolism
Malondialdehyde
/ metabolism
Membrane Proteins
/ genetics
NADPH Oxidase 2
/ genetics
NADPH Oxidase 4
/ genetics
Oxidative Stress
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Renal Insufficiency
/ genetics
Superoxide Dismutase
/ metabolism
HHcy
NOX2
NOX4
blood pressure
glomerular injury
hypertension
nephrin
Journal
American journal of hypertension
ISSN: 1941-7225
Titre abrégé: Am J Hypertens
Pays: United States
ID NLM: 8803676
Informations de publication
Date de publication:
31 12 2020
31 12 2020
Historique:
received:
11
11
2019
revised:
03
04
2020
accepted:
25
05
2020
pubmed:
3
6
2020
medline:
9
11
2021
entrez:
3
6
2020
Statut:
ppublish
Résumé
Hyperhomocysteinemia (HHcy) plays a synergistic role with hypertension in vascular injury; however, the relationship between HHcy and hypertension in renal injury remains unclear. Here, we sought to evaluate the relationship between HHcy and hypertension in the context of renal injury and to elucidate the mechanism of action underlying this relationship. Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were randomized into WKY, WKY + HHcy, SHR, and SHR + HHcy groups. Blood pressure, plasma homocysteine, serum malondialdehyde (MDA), serum superoxide dismutase (SOD), urinary albumin creatinine ratio (UACR), and glomerular filtration rate (GFR) were measured. Renal histopathology and expression levels of NOX2, NOX4, and nephrin in the kidneys were examined. The WKY + HHcy and SHR groups exhibited lower serum SOD and GFR levels, relative to the WKY group, along with higher levels of both serum MDA and UACR. Higher mRNA and protein expression levels of NOX2 and NOX4, along with lower expression levels of nephrin, were observed in the kidneys of WKY + HHcy and SHR rats, relative to WKY controls, respectively. Similar effects were observed in the SHR + HHcy group, relative to the SHR group and WKY + HHcy group, respectively. Periodic acid-Schiff staining showed an increase in the glomerular extracellular matrix in the WKY + HHcy and SHR + HHcy groups compared with their respective controls. HHcy appears to synergistically increase hypertensive renal damage by enhancing oxidative stress.
Sections du résumé
BACKGROUND
Hyperhomocysteinemia (HHcy) plays a synergistic role with hypertension in vascular injury; however, the relationship between HHcy and hypertension in renal injury remains unclear. Here, we sought to evaluate the relationship between HHcy and hypertension in the context of renal injury and to elucidate the mechanism of action underlying this relationship.
METHODS
Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were randomized into WKY, WKY + HHcy, SHR, and SHR + HHcy groups. Blood pressure, plasma homocysteine, serum malondialdehyde (MDA), serum superoxide dismutase (SOD), urinary albumin creatinine ratio (UACR), and glomerular filtration rate (GFR) were measured. Renal histopathology and expression levels of NOX2, NOX4, and nephrin in the kidneys were examined.
RESULTS
The WKY + HHcy and SHR groups exhibited lower serum SOD and GFR levels, relative to the WKY group, along with higher levels of both serum MDA and UACR. Higher mRNA and protein expression levels of NOX2 and NOX4, along with lower expression levels of nephrin, were observed in the kidneys of WKY + HHcy and SHR rats, relative to WKY controls, respectively. Similar effects were observed in the SHR + HHcy group, relative to the SHR group and WKY + HHcy group, respectively. Periodic acid-Schiff staining showed an increase in the glomerular extracellular matrix in the WKY + HHcy and SHR + HHcy groups compared with their respective controls.
CONCLUSIONS
HHcy appears to synergistically increase hypertensive renal damage by enhancing oxidative stress.
Identifiants
pubmed: 32484231
pii: 5850246
doi: 10.1093/ajh/hpaa086
doi:
Substances chimiques
Membrane Proteins
0
nephrin
0
Homocysteine
0LVT1QZ0BA
Malondialdehyde
4Y8F71G49Q
Creatinine
AYI8EX34EU
Superoxide Dismutase
EC 1.15.1.1
Cybb protein, rat
EC 1.6.3.-
NADPH Oxidase 2
EC 1.6.3.-
NADPH Oxidase 4
EC 1.6.3.-
Nox4 protein, rat
EC 1.6.3.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1127-1135Informations de copyright
© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.