Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9017898 | Toxicology and Applied Pharmacology | 2005 | 8 Pages |
Abstract
The present study was designed to evaluate the effects of peroxynitrite (ONOOâ), the product of superoxide and nitric oxide, on isolated segments of rat aorta. In the absence of any vasoactive agent, ONOOâ (from 10â8 to 10â4 M) failed to alter the basal tension. In phenylephrine (PE; 5 Ã 10â7 M)-precontracted rat aortic rings (RAR), ONOOâ elicited concentration-dependent relaxation at concentrations of from 10â8 to 10â4 M. The effective concentrations producing approximately 50% of maximal relaxation (ED50) to ONOOâ were 1.84 Ã 10â5 M and 1.96 Ã 10â5 M in intact and denuded RAR, respectively (P > 0.05). No significant differences in the relaxation responses were found between RAR with or without endothelium (P > 0.05). The presence of either 5 μM methylene blue (MB) or 5 μM 1H-[1,2,4]oxadiazolo-[4,3-α]quinoxalin-1-one (ODQ) significantly inhibited the relaxations induced by ONOOâ. Sildenafil (10â7 M), on the other hand, significantly potentiated the ONOOâ-induced relaxations. Tetraethylammonium chloride (T-2265) significantly decreased the ONOOâ-induced relaxations in a concentration-dependent manner. However, ONOOâ had no effect on RAR precontracted by high KCL (40 mM, n = 6, P > 0.05). Addition of calyculin A also significantly decreased the ONOOâ-induced relaxation in a dose-dependent manner. Furthermore, ONOOâ significantly inhibited calcium-induced contractions of K+-depolarized aortic rings in a concentration-related manner. Lastly, a variety of other pharmacological agents and antagonists including l-NMMA, l-arginine, indomethacin, atropine, naloxone, diphenhydramine, cimetine, glibenclamide, haloperidol, superoxide dismutase (SOD), and catalase did not influence the relaxant effects of ONOOâ on RAR. Our new results suggest that ONOOâ-triggered relaxation on rat aortic rings is mediated by elevation of cGMP levels, membrane hyperpolarization via K+-channel activation, activation of myosin phosphatase activity, and interference with calcium movement and cellular membrane Ca2+ entry.
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Authors
Jianfeng Li, Wenyan Li, Bella T. Altura, Burton M. Altura,