Effect of nitroxyl on the hamster retinal nitridergic pathway.
There is a growing body of evidence on the role of nitric oxide (NO) in retinal physiology. Recently, interest has developed in the functional role of an alternative redox form of NO, namely nitroxyl (HNO/NO(-)), because it is formed by a number of diverse biochemical reactions. The aim of the present report was to comparatively analyze the effect of HNO and NO on the retinal nitridergic pathway in the golden hamster. For this purpose, sodium trioxodinitrate (Angeli's salt) and diethylammonium (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA/NO) were used as HNO and NO releasers, respectively. Angeli's salt and DEA/NO significantly decreased nitric oxide synthase activity. In addition, Angeli's salt (but not DEA/NO) significantly decreased l-arginine uptake. DEA/NO significantly increased cGMP accumulation at low micromolar concentrations, while Angeli's salt affected this parameter with a threshold concentration of 200muM. Although Angeli's salt and DEA/NO significantly diminished reduced glutathione and protein thiol levels in a similar way, DEA/NO was significantly more effective than AS in increasing S-nitrosothiol levels. None of these compounds increased retinal lipid peroxidation. These results suggest that HNO could regulate the hamster retinal nitridergic pathway by acting through a mechanism that only partly overlaps with that involved in NO response.
Sáenz
Daniel A
DA
Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental, Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, CEFyBO, CONICET, Buenos Aires, Argentina.
Bari
Sara E
SE
Salido
Ezequiel
E
Chianelli
Mónica
M
Rosenstein
Ruth E
RE
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001120:Arginine / Q000378:metabolism; D006224:Cricetinae; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008647:Mesocricetus; D026602:Nitrergic Neurons / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D009573:Nitrites / Q000494:pharmacology; D009589:Nitrogen Oxides / Q000378:metabolism* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D026403:S-Nitrosothiols / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014795:Visual Pathways / Q000187:drug effects / Q000378:metabolism*
D000975:Antioxidants; D009573:Nitrites; D009589:Nitrogen Oxides; D000644:Quaternary Ammonium Compounds; D026403:S-Nitrosothiols; C406802:diethylammonium-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate; C021229:oxyhyponitrite; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D005978:Glutathione; C039900:nitroxyl; D006152:Cyclic GMP