TOXI 27 |
| Nitric oxide (NO) and cyclooxygenase (COX) signaling pathways interact in several ways that result in reciprocal regulation of each by the other. We study these phenomena in the vasculature, a site that depends on both for homeostasis. Examples include (i) characterisation of NO as a COX peroxidase substrate, (ii) COX-1 regulation of NO in platelets, (iii) COX-2 consumption of monocyte NO. More recently, interactions of COX and NO in the context of NSAID toxicity, a subject of intense interest in the media, were studied. In mice, acute hypertensive and pro-thrombotic activites of the COX-2 selective celecoxib were revealed only after in vivo inhibition of NO. In contrast, the non-selective indomethacin was hypertensive but anti-thrombotic in the absence of NO. In vitro myography confirmed the requirement for NOS and COX-2 for vasoconstriction. Since decreased vascular NO is known in arthritis, the risk of adverse events may be higher in this group. |
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Frontiers in Chemical Toxicology
1:00 PM-4:45 PM, Monday, August 20, 2007 BCEC -- 258C, Oral
Division of Chemical Toxicology |