Impaired expression of nitric oxide synthase in the gastric myenteric plexus of spontaneously diabetic rats.
OBJECTIVE
The mechanism responsible for defective gastric accommodation in diabetes is unknown. The aim of this study was to investigate if this abnormality is due to a defective nitric oxide pathway secondary to impaired nitric oxide synthase (NOS) expression in the gastric myenteric plexus.


METHODS
To test this hypothesis, we studied nonadrenergic, noncholinergic (NANC) relaxation, NOS activity, NADPH diaphorase histochemistry, NOS immunohistochemistry, NOS immunoblotting, and NOS messenger RNA expression in the gastric myenteric plexus of spontaneously diabetic biobreeding/Worcester (BB/W) rats. Age-matched nondiabetic Wistar rats were used as controls.


RESULTS
Gastric neuromuscular preparations from control rats showed a frequency-dependent NANC relaxation in response to transmural stimulation. This relaxation was markedly antagonized by N(G)-nitro-L-arginine-methyl ester, indicating mediation by the neuronal release of NO. The NANC relaxation in gastric muscle preparations obtained from diabetic BB/W rats was significantly impaired. The number of NOS-immunoreactive cells in the gastric myenteric plexus and the NOS activity were significantly reduced in diabetic BB/W rats, suggesting that NOS synthesis is impaired in diabetes. Northern blot analysis showed that the density of NOS messenger RNA bands at 9.5 kilobases was significantly reduced in the gastric tissues of diabetic BB/W rats.


CONCLUSIONS
These results indicate that gastric relaxation in diabetics is hampered mainly by impaired NOS expression in the gastric myenteric plexus.
Takahashi
T
T
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0362, USA.
Nakamura
K
K
Itoh
H
H
Sima
A A
AA
Owyang
C
C
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D009197:Myenteric Plexus / Q000201:enzymology / Q000503:physiopathology*; D009431:Neural Conduction; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D009599:Nitroprusside / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000201:enzymology / Q000503:physiopathology*
D009599:Nitroprusside; D019001:Nitric Oxide Synthase; D011493:Protein Kinase C