Mechanisms of gastroprotection by transdermal nitroglycerin in the rat.
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. 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 ml) of acidified bile salts (100 mg kg(-1) taurocholic acid in 150 mM HCl) or 50% ethanol. 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. 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. 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.
Calatayud
S
S
Department of Pharmacology, Faculty of Medicine, University of Valencia, Spain.
Sanz
M J
MJ
Canet
A
A
Bello
R
R
de Rojas
F D
FD
Esplugues
J V
JV
D000279:Administration, Cutaneous; D000818:Animals; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D007213:Indomethacin / Q000633:toxicity; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D005996:Nitroglycerin / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects
D009569:Nitric Oxide; D005996:Nitroglycerin; D007213:Indomethacin