1 Nitric oxide (NO) is an important mediator of gastric mucosal defense. Sildenafil (SILD), a cyclic GMP-specific phosphodiesterase inhibitor, promotes an increase in cGMP concentrations in the gastrointestinal tract. cGMP mediates many of the biological actions of NO. 2 We tested the hypothesis that SILD could increase mucosal defense against indomethacin-induced gastropathy in rats. 3 SILD (1, 4 or 10 mg kg À1 , p.o.) pretreatment significantly reduced (Po0.01) the gastric damage and the increase in gastric myeloperoxidase (MPO) activity elicited by indomethacin (20 mg kg À1 p.o.), with the maximal effect at the dose of 10 mg kg À1 . 4 L-NAME (3, 10 or 20 mg kg À1 , i.p.) dose dependently reversed the protective effects of SILD, an effect not seen when L-arginine (L-ARG) (200 mg kg À1 , i.p.) was co-administered with L-NAME. 5 Indomethacin-induced leukocyte adhesion, assessed by intravital microscopy, was decreased (Po0.01) by SILD, and this effect was reversed by L-NAME cotreatment. 6 Indomethacin elicited a decrease in gastric blood flow and in gastric PGE 2 levels. SILD was able to prevent the decrease in gastric blood flow (Po0.01), without diminishing the inhibitory effect of indomethacin on prostaglandin synthesis. 7 These results indicate that SILD, acting via NO-dependent mechanisms, prevents indomethacininduced gastropathy, possibly through a reduction of leukocyte adhesion and maintenance of gastric blood flow.

No abstract

No abstract

No abstract

We evaluated the effects of cyclooxygenase-2 (COX-2) selective inhibitors, COX-1 selective inhibitor, or COX non-selective inhibitor on gastric emptying and intestinal transit of liquids, and evaluated the effect of a COX-2 selective inhibitor on gastric tonus (GT). Male Wistar rats were treated per os with saline (control), rofecoxib, celecoxib, ketorolac, rofecoxib + ketorolac, celecoxib + ketorolac, or indomethacin. After 1 h, rats were gavage-fed (1.5 mL) with the test meal (5% glucose solution with 0.05 g mL(-1) phenol red) and killed 10, 20 or 30 min later. Gastric, proximal, medial or distal small intestine dye recovery (GDR and IDR, respectively) were measured by spectrophotometry. The animals of the other group were treated with i.v. valdecoxib or saline, and GT was continuously observed for 120 min using a pletismomether system. Compared with the control group, treatment with COX-2 inhibitors, alone or with ketocolac, as well as with indomethacin increased GDR (P < 0.05) at 10-, 20- or 30-min postprandial intervals. Ketorolac alone did not change the GDR, but increased the proximal IDR (P < 0.05) at 10 min, and decreased medial IDR (P < 0.05) at 10 and 20 min. Valdecoxib increased (P < 0.01) GT 60, 80 and 100 min after administration. In conclusion, COX-2 inhibition delayed the gastric emptying of liquids and increased GT in rats.