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Blood, 15 December 2006, Vol. 108, No. 13, pp. 4059-4062. Prepublished online as a Blood First Edition Paper on August 24, 2006; DOI 10.1182/blood-2006-02-005330.
Submitted February 23, 2006
Department of Medical Biochemistry and Immunology, University of Wales College of Medicine, Cardiff * Corresponding author; email: o-donnellvb{at}cardiff.ac.uk.
The cardiovascular safety of COX-2 selective and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) has recently been called into question. The factors that predispose to adverse events by NSAIDs are unknown. Since patients with arthritis have decreased nitric oxide (NO) bioavailability, the in vivo effects of NSAIDs on murine vascular tone and platelet activity in the presence/absence of NO were examined. Here we show that acute hypertensive and pro-thrombotic activities of the COX-2 selective inhibitor celecoxib are revealed only after in vivo inhibition of NO generation. The non-selective NSAID indomethacin was hypertensive but anti-thrombotic when NO was absent. In vitro myography of aortic rings confirmed that vasoconstriction required inhibition of both NOS and COX-2, and was abolished by supplementation with exogenous NO. These data indicate that NO suppresses vascular side-effects of NSAIDs, suggesting that risk will be greatest in patients with impaired vascular function associated with decreased NO bioavailability.
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