L-beta,beta-dimethylcysteine attenuates the haemodynamic responses elicited by systemic injections of peroxynitrite in anaesthetized rats.
1 There is direct chemical evidence that L-beta,beta-dimethylcysteine (L-penicillamine (L-PEN)) is a scavenger of peroxynitrite. The aim of this study was to determine whether L-PEN attenuates the haemodynamic responses elicited by peroxynitrite in pentobarbital-anaesthetized rats. 2 Peroxynitrite (1-20 micromol kg(-1), i.v.) elicited dose-dependent reductions in mean arterial blood pressure (MAP) and mesenteric and hindquarter vascular resistances. 3 L-PEN (2 mmol kg(-1), i.v.) elicited relatively minor but significant increases in MAP and vascular resistances. The initial reductions in MAP and vascular resistances elicited by peroxynitrite were not diminished after administration of L-PEN whereas they were much shorter in duration. As such, the total reductions in MAP and vascular resistances were markedly reduced by L-PEN. 4 The finding that L-PEN (2 mmol kg(-1), i.v.) did not affect the hypotensive or vasodilator responses elicited of the ATP-dependent potassium-channel agonist, cromakalim (3-18 microg kg(-1), i.v.), suggests that this dose of L-PEN is not a nonselective inhibitor of vasodilation. 5 These findings suggest that L-PEN may effectively scavenge peroxynitrite in vivo and/or interfere with the mechanisms by which peroxynitrite elicits its vasodilator responses.
Department of Physiology and Pharmacology, University of Georgia, Athens, GA, USA.
Jonathan E
JE
Graves
Neil W
NW
Kooy
Stephen J
SJ
Lewis
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure; D019806:Cromakalim / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D010396:Penicillamine / Q000494:pharmacology*; D030421:Peroxynitrous Acid / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation; D014655:Vascular Resistance; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D016166:Free Radical Scavengers; D014665:Vasodilator Agents; D019806:Cromakalim; D030421:Peroxynitrous Acid; D010396:Penicillamine