Reactive oxygen species (ROS) such as superoxide (O2-) generated by NAD(P)H oxidases have emerged as important molecules in blood pressure regulation. This study investigated the effect of apocynin and catalase on blood pressure and renal haemodynamic and excretory function in an L-NAME induced hypertension model. Forty Male Wistar-Kyoto (WKY) rats (n=8 per group) were treated with either: vehicle (WKY-C); L-NAME (WKY-L, 15 mg/kg/day in drinking fluid); WKY-L given apocynin to block NAD(P)H oxidase (WKY-LApo, 73 mg/kg/day in drinking water.); WKY-L given catalase to enhance ROS scavenging (WKY-LCat, 10000 U/kg/day i.p.); and WKY-L receiving apocynin plus catalase (WKY-LApoCat) daily for 14 days. L-NAME elevated systolic blood pressure (SBP), 116+/-1 to 181±4 mmHg, reduced creatinine clearance, 1.69+/-0.26 to 0.97+/-0.05 ml/min/kg and fractional sodium excretion, 0.84+/-0.09 to 0.55+/-0.09 % at day 14. Concomitantly, plasma malondialdehyde (MDA) increased six fold, while plasma total superoxide dismutase (T-SOD), plasma nitric oxide (NO) and plasma total antioxidant capacity (T-AOC) were decreased by 60-70 % and Nox 4 mRNA expression was increased 2-fold. Treatment with apocynin and catalase attenuated the increase in SBP and improved renal function, enhanced antioxidative stress capacity and reduced the magnitude of Nox4 mRNAs expression in the L-NAME treated rats. This study demonstrated that apocynin and catalase offset the development of L-NAME induced hypertension, renal dysfunction and reduced oxidative stress status, possibly contributed by a reduction in Nox4 expression during NOS inhibition. These findings would suggest that antioxidant compounds such as apocynin and catalase have potential in treating cardiovascular diseases.
- MeSH
- acetofenony farmakologie MeSH
- antioxidancia farmakologie MeSH
- hemodynamika MeSH
- hypertenze chemicky indukované farmakoterapie patofyziologie MeSH
- inhibitory enzymů toxicita MeSH
- katalasa farmakologie MeSH
- kombinovaná farmakoterapie MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- NADPH-oxidasa 4 metabolismus MeSH
- NG-nitroargininmethylester toxicita MeSH
- potkani inbrední WKY MeSH
- reaktivní formy kyslíku metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
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
High levels of reactive oxygen species (ROS), which may be associated with reduced sperm quality, can be detected during cryopreservation of sperm of some species. Our objective was to investigate whether the addition of antioxidants to cryopreservation extenders influenced post-thaw sperm characteristics and fertility in Acipenser dabryanus, Acipenser sinensis and Acipenser baerii. Prior to freezing, sperm samples were diluted with a base extender as control or in extender supplemented with catalase (CAT), glutathione (GSH), cysteine (NAC), ascorbic acid (VC) or their paired combinations. Protective concentrations of CAT, GSH and VC in the three species were 25 U/ml, 0.25-0.5 mg/ml and 0.5 mg/ml, respectively. Cysteine showed no protective effect against ROS. The addition of CAT, GSH and VC positively affected either acrosome or membrane integrity of post-thawed sperm in the three species, as well as spermatozoan motility in A. sinensis. The combination of antioxidants did not show a positive synergistic effect. This study suggested that the use of antioxidants in the cryopreservation of sturgeon sperm has potential to decrease intracellular ROS, and consequently preserve acrosome and membrane integrity, as well as spermatozoan motility.
- MeSH
- akrozom účinky léků MeSH
- antioxidancia farmakologie MeSH
- buněčná membrána účinky léků MeSH
- cystein farmakologie MeSH
- glutathion farmakologie MeSH
- katalasa farmakologie MeSH
- kryoprezervace metody veterinární MeSH
- kryoprotektivní látky farmakologie MeSH
- kyselina askorbová farmakologie MeSH
- motilita spermií účinky léků MeSH
- reaktivní formy kyslíku analýza MeSH
- ryby * MeSH
- spermie účinky léků MeSH
- uchování spermatu metody veterinární MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- ferrikyanidy farmakologie MeSH
- glycerolfosfáty metabolismus MeSH
- hnědá tuková tkáň metabolismus účinky léků MeSH
- inhibitory enzymů farmakologie MeSH
- katalasa farmakologie metabolismus MeSH
- peroxid vodíku metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- techniky in vitro MeSH
- MeSH
- azid sodný farmakologie MeSH
- calcimycin farmakologie MeSH
- dospělí MeSH
- katalasa farmakologie MeSH
- lidé MeSH
- N-formylmethionin-leucyl-fenylalanin farmakologie MeSH
- neutrofily fyziologie MeSH
- superoxiddismutasa farmakologie MeSH
- trombocyty fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- MeSH
- amitrol farmakologie MeSH
- katalasa antagonisté a inhibitory farmakologie MeSH
- králíci MeSH
- oční čočka enzymologie MeSH
- rohovka enzymologie účinky záření MeSH
- scavengery volných radikálů farmakologie MeSH
- ultrafialové záření MeSH
- xanthinoxidasa metabolismus účinky záření MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
