Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Akar, F; Uydes-Dosan, BS; Buharalioslu, CK; Abban, G; Heinemann, A; Holzer, P; Van de Voorde, J.
Protective effect of cromakalim and diazoxide, and proulcerogenic effect of glibenclamide on indomethacin-induced gastric injury.
EUR J PHARMACOL 1999 374: 461-470.
Doi: 10.1016%2FS0014-2999%2899%2900277-0
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- Co-Autor*innen der Med Uni Graz
- Heinemann Akos
- Holzer Peter
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- Abstract:
- We investigated the influences of the K+ channel opening drugs cromakalim and diazoxide and their blocker, glibenclamide, in indomethacin-induced gastric injury in rats. Cromakalim (0.1 and 0.3 mg/kg) and diazoxide (10 and 30 mg/kg) produced dose-dependent gastroprotection at doses that were also effective on the cardiovascular system. Glibenclamide reversed their gastroprotective effects and aggravated indomethacin-induced gastric damage by its own. Cromakalim (10(-9)-10(-5) M) and diazoxide (10(-9)-10(-4) M) relaxed noradrenaline pre-contracted gastric arteries (94.59+/-1.58% and 93.86+/-2.99%, respectively). Their relaxant effects were inhibited by glibenclamide (10(-5) M) but not by indomethacin (10(-5) M) and LG-nitro-L-arginine (10(-4) M). Cromakalim (0.1 and 0.3 mg/kg) did not change gastric mucosal blood flow but increased the gastric mucosal vascular conductance in anaesthetized rats as measured by the hydrogen gas clearance technique. Indomethacin increased myeloperoxidase activity in the gastric mucosa, an effect which was reversed by cromakalim and diazoxide. Glibenclamide abolished their effects on myeloperoxidase activity and, alone, increased this parameter. Additionally, indomethacin caused infiltration of neutrophils which was reduced by cromakalim and diazoxide in a glibenclamide sensitive manner. The effects of cromakalim and diazoxide on mucosal myeloperoxidase activity, neutrophil infiltration and gastric injury correlated with each other. The effects of diazoxide (30 mg/kg) and glibenclamide (10 mg/kg) on blood glucose level were not correlated with their effects on gastric injury. Taken together, K+ channel opening drugs show misoprostol-like protective effects in indomethacin-induced gastric injury which seems to be related to modulation of neutrophil function.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Arteries - drug effects
- Blood Glucose - drug effects
- Blood Pressure - drug effects
- Comparative Study - drug effects
- Cromakalim - pharmacology
- Diazoxide - pharmacology
- Dose-Response Relationship, Drug - pharmacology
- Gastric Mucosa - blood supply
- Gastrointestinal Agents - pharmacology
- Glyburide - pharmacology
- Hypoglycemic Agents - pharmacology
- Indomethacin - adverse effects
- Male - adverse effects
- Neutrophils - drug effects
- Peroxidase - drug effects
- Rats - drug effects
- Regional Blood Flow - drug effects
- Research Support, Non-U.S. Gov't - drug effects
- Stomach - drug effects
- Stomach Diseases - chemically induced
- Vasodilation - drug effects
- Vasodilator Agents - pharmacology