PMID- 32484231 OWN - NLM STAT- MEDLINE DCOM- 20211108 LR - 20211108 IS - 1941-7225 (Electronic) IS - 0895-7061 (Linking) VI - 33 IP - 12 DP - 2020 Dec 31 TI - Hyperhomocysteinemia-Induced Oxidative Stress Aggravates Renal Damage in Hypertensive Rats. PG - 1127-1135 LID - 10.1093/ajh/hpaa086 [doi] AB - 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. CI - (c) American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com. FAU - Gao, Ning AU - Gao N AD - Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China. FAU - Zhang, Yuzhen AU - Zhang Y AD - Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China. FAU - Li, Li AU - Li L AD - Department of Clinical Nutrition, the People's Hospital of Zhangqiu, Jinan, Shandong, China. FAU - Lei, Lei AU - Lei L AD - Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China. FAU - Cao, Ping AU - Cao P AD - Department of Geriatric Medicine, Tai'an City Central Hospital, Tai'an, Shandong, China. FAU - Zhao, Xuan AU - Zhao X AD - Department of Cardiovascular Medicine, People's Hospital of Dongying, Dongying, Shandong, China. FAU - Lin, Lin AU - Lin L AD - Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China. FAU - Xu, Rui AU - Xu R AD - Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Hypertens JT - American journal of hypertension JID - 8803676 RN - 0 (Membrane Proteins) RN - 0 (nephrin) RN - 0LVT1QZ0BA (Homocysteine) RN - 4Y8F71G49Q (Malondialdehyde) RN - AYI8EX34EU (Creatinine) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 1.6.3.- (Cybb protein, rat) RN - EC 1.6.3.- (NADPH Oxidase 2) RN - EC 1.6.3.- (NADPH Oxidase 4) RN - EC 1.6.3.- (Nox4 protein, rat) SB - IM MH - Albuminuria MH - Animals MH - Blood Pressure MH - Creatinine/urine MH - Glomerular Filtration Rate MH - Homocysteine/metabolism MH - Hyperhomocysteinemia/genetics/*metabolism/pathology MH - Hypertension/genetics/*metabolism/pathology MH - Kidney/*metabolism/pathology MH - Malondialdehyde/metabolism MH - Membrane Proteins/genetics/metabolism MH - NADPH Oxidase 2/genetics/metabolism MH - NADPH Oxidase 4/genetics/metabolism MH - *Oxidative Stress MH - Rats MH - Rats, Inbred SHR MH - Rats, Inbred WKY MH - Renal Insufficiency/genetics/*metabolism/pathology MH - Superoxide Dismutase/metabolism OTO - NOTNLM OT - HHcy OT - NOX2 OT - NOX4 OT - blood pressure OT - glomerular injury OT - hypertension OT - nephrin EDAT- 2020/06/03 06:00 MHDA- 2021/11/09 06:00 CRDT- 2020/06/03 06:00 PHST- 2019/11/11 00:00 [received] PHST- 2020/04/03 00:00 [revised] PHST- 2020/05/25 00:00 [accepted] PHST- 2020/06/03 06:00 [pubmed] PHST- 2021/11/09 06:00 [medline] PHST- 2020/06/03 06:00 [entrez] AID - 5850246 [pii] AID - 10.1093/ajh/hpaa086 [doi] PST - ppublish SO - Am J Hypertens. 2020 Dec 31;33(12):1127-1135. doi: 10.1093/ajh/hpaa086.