Mechanisms of gastroprotection by transdermal nitroglycerin in the rat
Por:
Calatayud, S, Sanz, M, Canet, A, Bello, R, de Rojas, F and Esplugues, J
Publicada:
1 jul 1999
Categoría:
Pharmacology
Resumen:
1 Nitric oxide (NO) donors prevent experimentally-induced gastric mucosal damage, but their clinical utility is limited by short duration of action or unsuitability of the pharmaceutical form employed. This study analyses the gastroprotection elicited by a clinically used mode of continuous administration of an NO donor, namely the nitroglycerin patch.
2 Application to rats of a transdermal patch that releases doses of nitroglycerin comparable to those used in man (40, 80, 160 and 400 ng min(-1) rat(-1)) reduced gastric damage induced by indomethacin (25 mg kg(-1), p.o. or s.c.). The nitroglycerin patch (160 ng min(-1) rat(-1)) also diminished damage by oral administration (1 mi) of acidified bile salts (100 mg kg(-1) taurocholic acid in 150 mM HCl) or 50% ethanol.
3 Transdermal nitroglycerin (160 ng min(-1) rat(-1)) did not influence basal gastric blood flow, as measured by lasser-doppler flowmetry, but prevented its reduction by indomethacin.
4 Transdermal nitroglycerin (160 ng min(-1) rat(-1)) prevented in vivo leukocyte rolling and adherence in the rat mesentery microvessels superfused with indomethacin, as evaluated by intravital microscopy.
5 The transdermal nitroglycerin patch protects the gastric mucosa from damage by mechanisms that involve maintenance of mucosal blood flow and reduction of leukocyte-endothelial cell interaction.
Bronze, Green Published
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