1. The aim of the present study was to assess the effects of the potent oxidant and nitrating agent peroxynitrite on the haemodynamic actions of the endothelium-derived S-nitrosothiol l-S-nitrosocysteine. 2. The haemodynamic actions of l-S-nitrosocysteine (12.5-100 nmol/kg, i.v.) were determined in pentobarbital-anaesthetized rats before and after the induction of tachyphylaxis to peroxynitrite achieved by giving 10 intravenous injections of a 10 μmol/kg dose. 3. l-S-Nitrosocysteine elicited dose-dependent reductions in mean arterial blood pressure and in hindquarter and mesenteric vascular resistance. 4. The l-S-nitrosocysteine-induced responses were substantially attenuated after administration of peroxynitrite. 5. We have reported previously that nitric oxide-mediated vasodilation is not diminished after the induction of tachyphylaxis to peroxynitrite. Taken together, these findings support the concept that peroxynitrite reduces the vasodilator actions of l-S-nitrosocysteine via oxidation and/or nitration of putative membrane-bound S-nitrosothiol recognition sites.
|Original language||English (US)|
|Number of pages||5|
|Journal||Clinical and Experimental Pharmacology and Physiology|
|State||Published - Dec 1 2005|
- Nitric oxide