Increased susceptibility of diabetic rat gastric mucosa to food deprivation during cold stress.
BACKGROUND
We investigated the mechanisms responsible for the increased susceptibility of diabetic rat gastric mucosa to damage inflicted by overnight food deprivation (18 h) and its worsening by the cold restraint stress (4 degrees C, 3 h).


METHODS
Gastric damage was measured in fasted animals, some of which were rendered diabetic by a single intraperitoneal injection of streptozotocin (STZ; 70 mg/kg) 5 weeks before experiments (STZ 5W).


RESULTS
STZ 5W rodents showed a number of hemorrhagic lesions in corpus mucosa (26. 8 +/- 5.2 mm(2)) which could be prevented by insulin or nitric oxide synthase (NOS) inhibitors: aminoguanidine or L-NAME (N(omega)-nitro-L-arginine methyl ester). Mucosal injury was further aggravated by low temperature (51.1 +/- 7.8 mm(2)), the damage ameliorated by insulin, aminoguanidine, or L-NAME. The salutary actions of L-NAME were L-arginine sensitive. Low temperature and L-NAME did not significantly influence the gastric secretory parameters in normal rats. On the other hand, L-NAME and aminoguanidine counteracted the attenuation of gastric juice acidity and acid output in STZ 5W rodents. Blood plasma nitrite and nitrate levels and outputs in gastric juice were augmented in STZ 5W animals in comparison to controls. The total activities of NOS including inducible NOS but not constitutive NOS were markedly enhanced by fasting and cold restraint in gastric mucosa of STZ 5W animals (2.2- and 3.7- or 2.4- and 17.9-fold respectively).


CONCLUSIONS
Stressful stimuli, such as food bereavement and cold challenge contribute to the elevated susceptibility of diabetic gastric mucosa to damage, even though the main aggressive factor, i.e., gastric acid secretion, is attenuated. The enhanced production of nitric oxide by inducible NOS during food deprivation and cold exposure seems to play an important role in gastric mucosal integrity disturbances during diabetes.
Korolkiewicz
R
R
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Kyoto, Japan.
Tashima
K
K
Kubomi
M
M
Kato
S
S
Takeuchi
K
K
D000818:Animals; D003080:Cold Temperature / Q000009:adverse effects*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D004198:Disease Susceptibility; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005508:Food Deprivation; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006146:Guanidines / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D013312:Stress, Physiological / Q000150:complications* / Q000378:metabolism / Q000473:pathology
D004791:Enzyme Inhibitors; D006146:Guanidines; D007004:Hypoglycemic Agents; D007328:Insulin; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester