Masumi Yoshida, Kazuhide Inaguma and Mikio Ito*
Department of Pharmacology, Faculty of Pharmacy, Meijo University, 150
Yagotoyama, Tenpaku-ku, Nagoya 468 - 8503, Japan
* To whom correspondence should be addressed.
Abstract: In the present study, we investigated the susceptibility
to restraint plus water-immersion stress (RWIS) in rats with daunomycin-induced
nephrosis in comparison to that in normal rats. The severity of RWIS-induced
gastric lesions was significantly less in nephrotic rats on the 20th and
40th days after a single i.v. injection of daunomycin (12 mg/kg) than in
the respective control rats. Acid secretion in pylorus-ligated rats significantly
decreased under the 3-h stress. On the 20th day after treatment with daunomycin,
acid secretion was significantly less in nephrotic rats than in control
rats under both stress and unstressed conditions. Pretreatment of normal
rats with methylene blue, a guanylate cyclase inhibitor, or phenylephrine,
a vasoconstrictor, significantly prevented the stress-induced gastric lesions
and decreased acid secretion. Nω-Nitro-l-arginine methyl
ester, a nitric oxide (NO) synthase inhibitor, prevented the stress-induced
gastric lesion formation only. These results indicate that nephrotic rats
are more resistant to RWIS-induced gastric lesions than normal rats. In
addition, these results suggest that the decrease in acid secretion related
to the decrease in the release of NO from endothelial cells may contribute,
at least in part, to the prevention of the stress-induced gastric lesion
formation in nephrotic rats.
Keywords: Nephrosis, Stress, Gastroprotection, Gastric secretion