Anning, Peter Brian, Coles, Barbara, Morton, Jonathan, Wang, Haibin, Uddin, Jashim, Morrow, Jason D., Dey, Sudhansu K., Marnett, Lawrence J. and O'Donnell, Valerie Bridget ![]() |
Abstract
The cardiovascular safety of COX-2 selective and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) has recently been called into question. The factors that predispose to adverse events by NSAIDs are unknown. Because 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 or absence of NO were examined. Here, we show that acute hypertensive and prothrombotic activities of the COX-2-selective inhibitor celecoxib are revealed only after in vivo inhibition of NO generation. The nonselective NSAID indomethacin was hypertensive but antithrombotic 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.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Medicine Systems Immunity Research Institute (SIURI) |
Publisher: | American Society of Hematology |
ISSN: | 0006-4971 |
Last Modified: | 31 Jan 2025 22:22 |
URI: | https://orca.cardiff.ac.uk/id/eprint/215 |
Citation Data
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