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Sildenafil prevents indomethacin-induced gastropathy in rats: role of leukocyte adherence and gastric blood flow.

Lookup NU author(s): Dr Henrique De Paula LemosORCiD

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Abstract

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. We tested the hypothesis that SILD could increase mucosal defense against indomethacin-induced gastropathy in rats. SILD (1, 4 or 10 mg kg(-1), p.o.) pretreatment significantly reduced (P < 0.01) the gastric damage and the increase in gastric myeloperoxidase (MPO) activity elicited by indomethacin (20 mg kg(-1) p.o.), with the maximal effect at the dose of 10 mg kg(-1). L-NAME (3, 10 or 20 mg kg(-1), i.p.) dose dependently reversed the protective effects of SILD, an effect not seen when L-arginine (L-ARG) (200 mg kg(-1), i.p.) was co-administered with L-NAME. Indomethacin-induced leukocyte adhesion, assessed by intravital microscopy, was decreased (P < 0.01) by SILD, and this effect was reversed by L-NAME cotreatment. Indomethacin elicited a decrease in gastric blood flow and in gastric PGE2 levels. SILD was able to prevent the decrease in gastric blood flow (P < 0.01), without diminishing the inhibitory effect of indomethacin on prostaglandin synthesis. These results indicate that SILD, acting via NO-dependent mechanisms, prevents indomethacin-induced gastropathy, possibly through a reduction of leukocyte adhesion and maintenance of gastric blood flow.

Publication metadata

Author(s): Santos CL, Souza MH, Gomes AS, Lemos HP, Santos AA, Cunha FQ, Wallace JL

Publication type: Article

Publication status: Published

Journal: British Journal of Pharmacology

Year: 2005

Volume: 146

Issue: 4

Pages: 481-486

Print publication date: 01/10/2005

Online publication date: 29/01/2009

ISSN (print): 0007-1188

ISSN (electronic): 1476-5381

Publisher: Wiley

URL: http://dx.doi/10.1038/sj.bjp.0706361

DOI: 10.1038/sj.bjp.0706361

PubMed id: 16113693

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