L-arginine is a substrate for nitric oxide synthase (NOS) responsible for the production of NO. This investigation studied the effect of apocynin, an NADPH oxidase inhibitor and catalase, an H2O2 scavenger on L-arginine induced oxidative stress and hypotension. Forty Wistar-Kyoto rats were treated for 14 days with vehicle, L-arginine (12.5mg/ml p.o.), L-arginine+apocynin (2.5mmol/L p.o.), L-arginine+catalase (10000U/kg/day i.p.) and L-arginine plus apocynin+catalase respectively. Weekly renal functional and hemodynamic parameters were measured and kidneys harvested at the end of the study for histopathological and renal NADPH oxidase 4 (Nox4) assessments. L-arginine administration in normotensive rats decreased systolic blood pressure (120±2 vs 91±2mmHg) and heart rate (298±21 vs 254±15b/min), enhanced urinary output (21.5±4.2 vs 32±1.9ml/24h , increased creatinine clearance (1.72±0.56 vs 2.62±0.40ml/min/kg), and fractional sodium excretion (0.88±0.16 vs 1.18±0.16 %), caused proteinuria (28.10±1.93 vs 35.26±1.69mg/kg/day) and a significant decrease in renal cortical blood perfusion (292±3 vs 258±5bpu) and pulse wave velocity (3.72±0.20 vs 2.84±0.13m/s) (all P<0.05). L-arginine increased plasma malondialdehyde (by ~206 % P<0.05) and NO (by~51 %, P<0.05) but decreased superoxide dismutase (by~31 %, P<0.05) and total antioxidant capacity (by~35 %, P<0.05) compared to control. Renal Nox4 mRNA activity was approximately 2.1 fold higher (P<0.05) in the L-arginine treated rats but was normalized by apocynin and apocynin plus catalase treatment. Administration of apocynin and catalase, but not catalase alone to rats fed L-arginine, restored the deranged renal function and structure, prevented hypotension and enhanced the antioxidant capacity and suppressed Nox4 expression. These findings suggest that apocynin and catalase might be used prophylactically in states of oxidative stress.
- MeSH
- acetofenony farmakologie MeSH
- analýza pulzové vlny metody MeSH
- antioxidancia farmakologie MeSH
- arginin farmakologie MeSH
- hypotenze chemicky indukované farmakoterapie metabolismus patologie MeSH
- katalasa farmakologie MeSH
- krevní tlak účinky léků MeSH
- krysa rodu rattus MeSH
- ledviny účinky léků metabolismus patologie MeSH
- modely nemocí na zvířatech MeSH
- NADPH-oxidasa 4 metabolismus MeSH
- oxidační stres účinky léků MeSH
- potkani inbrední WKY MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- anestezie * metody škodlivé účinky využití MeSH
- chirurgická rána * chirurgie komplikace terapie MeSH
- hojení ran fyziologie imunologie MeSH
- homeostáza fyziologie imunologie účinky léků MeSH
- hyperglykemie diagnóza etiologie terapie MeSH
- hypokalemie diagnóza etiologie terapie MeSH
- hyponatremie diagnóza etiologie terapie MeSH
- hypotenze diagnóza metabolismus terapie MeSH
- hypovolemie diagnóza etiologie terapie MeSH
- intravenózní infuze metody využití MeSH
- kongresy jako téma MeSH
- lidé MeSH
- pooperační komplikace * diagnóza etiologie prevence a kontrola MeSH
- rány a poranění komplikace patofyziologie terapie MeSH
- statistika jako téma MeSH
- syndrom dechové tísně diagnóza etiologie prevence a kontrola MeSH
- Check Tag
- lidé MeSH
- MeSH
- hypertenze maligní komplikace MeSH
- hypotenze etiologie metabolismus MeSH
- lidé MeSH
- postprandiální období MeSH
- Check Tag
- lidé MeSH