Interaction between peroxynitrite and L-cysteine: effects on rat aorta.
In rings of rat aorta previously exposed to peroxynitrite (1 mM), L-cysteine and its analogues containing, but not those lacking, a thiol group produced a powerful transient relaxation. This relaxation is likely to result from the release of nitric oxide from a nitrated/nitrosated compound formed following reaction of peroxynitrite with a component of the tissue or bathing medium. Furthermore, when peroxynitrite was pre-mixed with L-cysteine a new relaxant species was formed. Analogues of L-cysteine with a free thiol reacted with peroxynitrite to form species with similar relaxant potencies. Analogues lacking a thiol formed products with relaxant activity, but less than with L-cysteine. Analogues with a free amino but no thiol or carboxylic functions formed products with potencies similar to those lacking only the thiol. If the amino is substituted and the thiol removed, no relaxant activity was generated. Thus, peroxynitrite reacts with L-cysteine to form a novel relaxant whose activity derives mainly from formation of its S-nitrosothiol, with a lesser component perhaps from an N-nitroso derivative.
Dowell
F J
FJ
Clinical Research Initiative, University of Glasgow, UK. f.dowell@bio.gla.ac.uk
Martin
W
W
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology*; D004347:Drug Interactions; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009566:Nitrates / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D009566:Nitrates; D016877:Oxidants; C039642:peroxynitric acid; D003545:Cysteine