NicOx à l'ACC : présentation plus complète


In pre-contracted hIMA, endothelium-dependent vasorelaxation (acetylcholine) was reduced in comparison to the endothelium-independent (sodium nitroprusside) response. Accordingly, electron microscopy showed cellular abnormalities such as intima hyperplasia and endothelial cell degeneration. Naproxcinod (10 nM - 100 mM) caused a NO-mediated concentration-dependent relaxation (Emax= -52.4±6.9%, p<0.05 vs. control, n=6). Conversely, naproxen caused a slight but significant vasoconstriction (Emax=8±4%, p<0.05 vs. control, n=6). In non-precontracted hIMA, naproxcinod and the selective COX-1 inhibitor SC-560 showed no effect on vascular tone, while naproxen (Emax=17±2.7%, n=12), ibuprofen (Emax=8.8±2.3%, n=4) and rofecoxib (Emax=6.8±1.7%, n=4) caused a mild but significant vasoconstriction (p<0.05 vs. control).


Cyclooxygenase inhibition in arteries with endothelial dysfunction results in vasoconstriction, suggesting an important role of COX-derived prostaglandins (likely from COX-2) in the regulation and maintenance of vascular tone.

Nitric oxide donation from naproxcinod suppresses the vasoconstricting effect due to COX inhibition.

In cardiovascular diseases accompanied by endothelial dysfunction, naproxcinod may compensate NSAID-mediated interference with vascular homeostasis through its ability to release NO.

NO donation may explain, at least in part, why naproxcinod is less likely than naproxen to increase blood pressure in hypertensive patients with osteoarthritis (White et al, 2009).

Source :
Nitric Oxide Donation From The Cinod Naproxcinod Counteracts Cyclooxygenase Inhibition-dependent Contraction In Human Mammary Arteries

e-Abstract : 1274-351
Authors : Manlio Bolla, Alessandra Poggi, Barbara Vergani, Guido Gelpi, Julio Padron, Daniela Miglietta, NicOx Research, Milan, Italy, NicOx SA, Sophia Antipolis, France

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