C-type natriuretic-peptide-potentiated relaxation response of gastric smooth muscle in streptozotocin-induced diabetic rats

Abstract

AIM:To study the sensitivity of gastric smooth muscle to C-type natriuretic peptide (CNP) in streptozotocin (STZ)-induced diabetic rats. METHODS:The spontaneous contraction of a gastric smooth muscle strip was recorded by using physiological methods in rats. The expressions of CNP and natriuretic peptide receptor-B (NPR-B) in gastric tissue were examined by using immunohistochemistry techniques in the diabetic rat. RESULTS:At 4 wk after injection of STZ and vehicle, the frequency of spontaneous contraction of gastric smooth muscle was significantly reduced in diabetic rats, and the frequency was decreased from 3.10 ± 0.14 cycle/min in controls to 2.23 ± 0.13 cycle/min (n = 8 , P < 0 . 0 1 ) . H o w e ve r, t h e a m p l i t u d e o f spontaneous contraction was not significant different from the normal rat. CNP significantly inhibited spontaneous contraction of gastric smooth muscle in normal and diabetic rats, but the inhibitory effect was significantly potentiated in the diabetic rats. The amplitudes of spontaneous contraction were suppressed by 75.15% ± 0.71% and 58.92% ± 1.32% while the frequencies were decreased by 53.33% ± 2.03% and 26.95% ± 2.82% in diabetic and normal rats, respectively (n = 8, P < 0.01). The expression of CNP in gastric tissue was not changed in diabetic rats, however the expression of NPR-B was significantly increased in diabetic rats, and the staining indexes of NPR-B were 30.67 ± 1.59 and 17.63 ± 1.49 in diabetic and normal rat, respectively (n = 8, P < 0.01). CONCLUSION:The results suggest that CNP induced an inhibitory effect on spontaneous contraction of gastric smooth muscle, potentiated in diabetic rat via up-regulation of the natriuretic peptides-NPR-Bparticulate guanylyl cyclase-cyclic GMP signal pathway.

Delayed gastric emptying in diabetic rats caused by decreased expression of cystathionine gamma lyase and H2S synthesis: in vitro and in vivo studies

“…Cai et al . have shown that only the frequency of spontaneous contraction was significantly decreased in diabetic rats . Our findings are in agreement with Cai et al .…”

“…Cai et al have shown that only the frequency of spontaneous contraction was significantly decreased in diabetic rats. 31 Our findings are in agreement with Cai et al report showed that the frequency of spontaneous contractions of gastric smooth muscle strips in diabetic rats was significantly lower than in normal rats while the amplitude was not significantly affected in diabetic rats. The present research showed that NaHS at 100 lmol/L was increased the frequency and tension of spontaneous contraction of gastric muscle strips in diabetic rats.…”

Electroacupuncture promotes the gastrointestinal motility of diabetic mice by CNP/NPR‐B‐cGMP and PDE3A‐cGMP signaling

“…When CNP binds to NPR-B, it could activate GC to catalyze the transformation of cGMP from GTP and then cause a relaxation of the gastric and colonic smooth muscles. [17][18][19] There was a report which confirmed that inhibitory effect of CNP on gastric smooth muscle was strengthened in diabetic rat via up-regulation of cGMP, 20 are the most common isoforms in GI tract, and PDE3 is a main regulator of murine gastrointestinal circular muscle contraction, while higher concentration of PDE2 could partly influence the gut motility. 22,23 Cai et al 24 confirmed only the expression level of PDE3 was decreased in gastric smooth muscle of diabetic rats.…”

“…When CNP binds to NPR‐B, it could activate GC to catalyze the transformation of cGMP from GTP and then cause a relaxation of the gastric and colonic smooth muscles . There was a report which confirmed that inhibitory effect of CNP on gastric smooth muscle was strengthened in diabetic rat via up‐regulation of cGMP, but the effect of CNP on colon in the diabetic model has not been explored. In the present study, we proved that the CNP/NPR‐B‐cGMP signaling was up‐regulated both in the stomach and colon of diabetic mice with GI motility disorders.…”

Significance of dynamic changes in gastric smooth muscle cell apoptosis, PI3K-AKT-mTOR and AMPK-mTOR signaling in a rat model of diabetic gastroparesis

“…The breeding conditions remained unchanged. At 7 days post-injection, tail vein blood was collected and the success of the model was determined based on a glucose concentration >350 mg/dL (12,13). The model rats were randomly divided into groups of 10, including a normal control (NC) group and diabetic model (DM) groups examined 2 weeks (DM2W), 4 weeks (DM4W) and 6 weeks (DM6W) later.…”