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1 AZD3582 [4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl)propanoate] is a COX-inhibiting nitric oxide donor that inhibits COX-1 and COX-2. It is as effective as naproxen in models of pain and inflammation, but causes less gastroduodenal damage. Nitric oxide (NO) is generated from AZD3582 in vitro, and this study sought to show that the drug donates NO in vivo. 2 In anaesthetised male New Zealand white rabbits, the endogenous NO concentration in exhaled air was reduced by NG-nitro-L-arginine methyl ester (L-NAME) (30 mg kg− 1 i.v.) from 33.5±1.0 ppb (mean±s.e.m.; n=6 per group) to 3.0±1.0 ppb, while increasing blood pressure and reducing heart rate. AZD3582 (0.2, 0.6, 2.0 or 6.0 μmol kg− 1 min− 1) given 30 min after L-NAME increased the concentration of NO in exhaled air (P |
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