Calatayud S, Sanz M J, Canet A, Bello R, de Rojas F D, Esplugues J V
Department of Pharmacology, Faculty of Medicine, University of Valencia, Spain.
Br J Pharmacol. 1999 Jul;127(5):1111-8. doi: 10.1038/sj.bjp.0702649.
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.
一氧化氮（NO）供体可预防实验性诱导的胃黏膜损伤，但其临床应用因作用持续时间短或所用药物剂型不合适而受到限制。本研究分析了临床使用的NO供体持续给药方式（即硝酸甘油贴片）所引发的胃保护作用。给大鼠应用释放与人用剂量相当的硝酸甘油（40、80、160和400 ng min⁻¹大鼠⁻¹）的透皮贴片，可减轻吲哚美辛（25 mg kg⁻¹，口服或皮下注射）诱导的胃损伤。硝酸甘油贴片（160 ng min⁻¹大鼠⁻¹）还可减轻口服（1 ml）酸化胆盐（100 mg kg⁻¹牛磺胆酸溶于150 mM HCl）或50%乙醇所致的损伤。通过激光多普勒血流仪测量，透皮硝酸甘油（160 ng min⁻¹大鼠⁻¹）不影响基础胃血流量，但可防止吲哚美辛所致的胃血流量减少。通过活体显微镜评估，透皮硝酸甘油（160 ng min⁻¹大鼠⁻¹）可防止在体白细胞在灌注吲哚美辛的大鼠肠系膜微血管中滚动和黏附。透皮硝酸甘油贴片通过维持黏膜血流量和减少白细胞与内皮细胞相互作用的机制保护胃黏膜免受损伤。
