1. Volume 132, Issue 2, Pages 709-719 (February 2007)
Nitroflurbiprofen, a Nitric Oxide-Releasing Cyclooxygenase Inhibitor, Improves Cirrhotic Portal Hypertension in Rats 
Wim Laleman, Lien Van Landeghem, Ingrid Van der Elst, Marcel Zeegers, Johan Fevery, Frederik Nevens 
Gastroenterology 
Volume 132, Issue 2, Pages (February 2007)
DOI: /j.gastro
Copyright © 2007 AGA Institute Terms and Conditions

2. Figure 1
Effect of nitroflurbiprofen, flurbiprofen, and vehicle on portal pressure (A), mean arterial pressure (B), and mesenteric blood flow (C) in the different treatment groups of cirrhotic rats (n = 8/group). *P < .005 vs vehicle-treated cirrhotic rats. TAA, thioacetamide; NO-flurbi, nitroflurbiprofen; flurbi, flurbiprofen.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2007 AGA Institute Terms and Conditions

3. Figure 2
Nitroflurbiprofen and flurbiprofen reduce the total intrahepatic vascular resistance in the perfused TAA cirrhotic rat liver (*P < .001 normal vs TAA + vehicle, **P < .001 TAA + flurbi and TAA + NO-flurbi vs normal and TAA + vehicle). TAA, thioacetamide; NO-flurbi, nitroflurbiprofen; flurbi, flurbiprofen.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2007 AGA Institute Terms and Conditions

4. Figure 3
(A) Nitroflurbiprofen and flurbiprofen improve the impaired vasodilatory response to acetylcholine (endothelial dysfunction) in the TAA cirrhotic rat liver (*P < .001 TAA + vehicle vs all). (B) TXB2 production after acetylcholine in TAA cirrhotic rat liver preincubated with nitroflurbiprofen (n = 5), flurbiprofen (n = 5), or vehicle (n = 5) and normal liver with vehicle (n = 5) (*P < .001 TAA + vehicle vs all other groups, **P < .001 TAA + nitroflurbi and flurbi vs normal and TAA + vehicle). TAA, thioacetamide; NO-flurbi, nitroflurbiprofen; flurbi, flurbiprofen.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2007 AGA Institute Terms and Conditions

5. Figure 4
Improvement of endothelial dysfunction by flurbiprofen in the TAA cirrhotic rat is attenuated by L-NAME, a known NOS-inhibitor, suggesting an interaction between COX metabolites and NOS (TAA + flurbi vs TAA + flurbi + L-NAME, *P < .05 at 10−6 and 10−7 mol/L acetylcholine). TAA, thioacetamide; flurbi, flurbiprofen; L-NAME, NG-nitro-L-arginine-methyl ester; COX, cyclooxygenase; NOS, nitric oxide synthase.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2007 AGA Institute Terms and Conditions

6. Figure 5
Nitroflurbiprofen, more than flurbiprofen, attenuates the intrahepatic hyperresponsiveness to methoxamine (*P < .001 TAA + vehicle vs all other groups, **P ≤ .05 TAA + flurbiprofen vs TAA + nitroflurbiprofen). TAA, thioacetamide; NO-flurbi, nitroflurbiprofen; flurbi, flurbiprofen; MTX, methoxamine; PP, perfusion pressure.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2007 AGA Institute Terms and Conditions

7. Figure 6
(A) U44619, a TXA2-analogue, promotes contraction in HSCs, which is dose dependently decreased following addition of increasing concentration of SQ29,548, a TXA2-receptor antagonist (*P < .05 vs U44619 alone, **P < μmol/L SQ29,548 vs 2.5 μmol/L SQ29,548). (B) Nitroflurbiprofen dose dependently inhibits FCS-promoted HSC contraction (*P < .001 vs FCS alone). flurbi, flurbiprofen; SQ, SQ29,548; FCS, fetal calf serum.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2007 AGA Institute Terms and Conditions

8. Figure 7
Serum (A) (n = 8/group) and hepatic (B) levels (n = 6/group) of nitrite/nitrate in the 3 different groups (*P = .005 vs others). NOx, nitrite/nitrate; TAA, thioacetamide; NO-flurbi, nitroflurbiprofen; flurbi, flurbiprofen.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2007 AGA Institute Terms and Conditions

9. Figure 8
Evaluation of gastrointestinal ulcerogenicity of the different treatment groups. (A) TAA + vehicle (n = 8). (B) TAA + nitroflurbiprofen (n = 8). (C) TAA + flurbiprofen (n = 8). A representative excised stomach is shown; ulcers are demarcated by a white arrow. (D) Dark colored tarry stools in the gut of a rat treated with flurbiprofen, suggestive of gastrointestinal bleeding. TAA, thioacetamide; NO-flurbi, nitroflurbiprofen; flurbi, flurbiprofen.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2007 AGA Institute Terms and Conditions

10. Figure 9
Suggested pathogenetic mechanism through which TXA2 exerts control on NO production. Stimulation of cyclooxygenases (COX) leads to increased TXA2-production, which, besides a direct paracrine effect on the hepatic stellate cell, also decreases Akt-stimulated activation of NO synthase (eNOS) and downstream signalling pathways. Soluble guanylate cyclase; sGC.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2007 AGA Institute Terms and Conditions