Mechanisms of gastroprotection by transdermal nitroglycerin in the rat

1 Nitric oxide (NO) donors prevent experimentally-induced gastric mucosal d amage, 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 administ ration of an NO donor, namely the nitroglycerin patch. 2 Application to rats of a transdermal patch that releases doses of nitrogl ycerin 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 dam age by oral administration (1 mi) of acidified bile salts (100 mg kg(-1) ta urocholic acid in 150 mM HCl) or 50% ethanol. 3 Transdermal nitroglycerin (160 ng min(-1) rat(-1)) did not influence basa l gastric blood flow, as measured by lasser-doppler flowmetry, but prevente d its reduction by indomethacin. 4 Transdermal nitroglycerin (160 ng min(-1) rat(-1)) prevented in vivo leuk ocyte rolling and adherence in the rat mesentery microvessels superfused wi th indomethacin, as evaluated by intravital microscopy. 5 The transdermal nitroglycerin patch protects the gastric mucosa from dama ge by mechanisms that involve maintenance of mucosal blood flow and reducti on of leukocyte-endothelial cell interaction.