Nitric oxide-mediated neurotransmission is attenuated in the anococcygeus muscle from diabetic rats

Way, Kerrie J.; Reid, Julianne J.

doi:10.1007/s001250050099

Cited by 5 publications

(3 citation statements)

References 19 publications

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“…Moreover, the inhibition of the nicotineinduced relaxation from diabetic rats was not a result of diminished reactivity of the smooth muscle to NO, since relaxation induced by the NO-donor, nitroprusside was not significantly affected. This observation contrasts with recent findings on the mechanisms underlying the attenuated NANC-relaxation in the anococcygeus muscle of diabetic rats, where reduced responses to nitroprusside were observed (Way & Reid, 1994). The present findings therefore suggest an impairment in the pre-junctional neuronal synthesis or release of NO in the duodenum of diabetic rats.…”

Section: Discussioncontrasting

confidence: 99%

Impairment of nitrergic‐mediated relaxation of rat isolated duodenum by experimental diabetes

Martínez-Cuesta

Massuda

Whittle

et al. 1995

British J Pharmacology

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Diabetes mellitus is associated with changes in gastrointestinal motility. The effects of experimental diabetes, induced by streptozotocin administration to rats 3–4 weeks previously, on the nitric oxide (NO)‐mediated (nitrergic) relaxation of the duodenum have now been investigated. The non‐adrenergic, non‐cholinergic (NANC) relaxation of the isolated duodenum induced by nicotine (0.3 – 10 μm) or the nicotinic agonist, 1,1‐dimethyl‐4‐phenylpiperazinium (DMPP; 10 μm) was inhibited by the NO synthase inhibitor, NG‐nitro‐l‐arginine (3–100 μm). This nitrergic relaxation induced by nicotine or DMPP of the duodenum from diabetic rats was substantially smaller than that of the tissue from control rats. By contrast, the relaxation of the duodenum from diabetic rats to the NO donor, nitroprusside (0.3–10 μm) was similar to that of control tissue, whereas the relaxation to ATP (0.1–3 μm) was enhanced to a small but significant degree. Incubation of duodenal tissue from control rats at 4°C for 72 h, which leads to neuronal disruption, significantly attenuated the relaxation to nicotine or DMPP whereas the relaxation induced by nitroprusside or ATP was not affected. Comparable cold‐storage did not affect the endothelium‐dependent relaxation of rat aortic rings induced by acetylcholine (0.01–2 μm). The calcium‐dependent NO synthase activity in duodenal tissue, determined by the conversion of radiolabelled l‐arginine to citrulline, was significantly reduced in cold‐stored tissue and in tissue obtained from diabetic rats. These findings in the rat duodenum indicate that a reduction in intestinal NO synthase activity is associated with an impairment of the NANC relaxation. A defect in the intestinal nitrergic innervation could thus contribute to the motility dysfunction observed in diabetes.

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Section: Discussioncontrasting

confidence: 99%

Impairment of nitrergic‐mediated relaxation of rat isolated duodenum by experimental diabetes

Martínez-Cuesta

Massuda

Whittle

et al. 1995

British J Pharmacology

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“…A similar nitrergic dysfunction accompanying diabetes had already been reported in several STZ-induced and spontaneous animal models for type-1 diabetes in the stomach, 10,[12][13][14]16 the duodenum 9,11 and the anococcygeus muscle. 26 Our results confirm that nitrergic motor control is also impaired in the jejunum of the spontaneously diabetic rat. Although we observed a decreased relaxatory response to administration of a maximal dose of the NO-donor NG, the decrease was modest (20%) and seems insufficient to explain the impaired nitrergic relaxation.…”

Section: Discussionsupporting

confidence: 82%

Characterization of myenteric neuropathy in the jejunum of spontaneously diabetic BB‐rats

Zandecki

Berghe

Depoortere

et al. 2008

Neurogastroenterology Motil

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Decreased gastric expression and function of neuronal nitric oxide synthase (nNOS) has been proposed as a potential mechanism underlying diabetic gastroparesis. As gastric nNOS expression is vagally controlled, these changes might occur secondarily to vagal neuropathy. In addition, it is unclear whether other inhibitory neurotransmitters are also involved. We used the type 1 diabetic BioBreeding (BB)-rat model to study jejunal motor control and nNOS expression, which is independent of the vagus. Jejunal segments were used for in vitro contractility studies, and measurement of nNOS expression after 8 or 16 weeks of diabetes compared with age- and sex-matched controls. Unlike electrical field stimulation and acetylcholine (ACh)-induced contractions, non-adrenergic non-cholinergic (NANC) relaxations were significantly reduced in diabetic rats. In contrast to control rats, NANC relaxations in diabetic rats were N(omega)-nitro-L-arginine methyl ester (L-NAME) insensitive. Jejunal nNOS expression was significantly decreased in diabetic rats. Both in diabetic and in control animals, L-NAME resistant relaxations were sensitive to P(2)-receptor antagonists. In the jejunum of spontaneously diabetic rats, decreased nitric oxide responsiveness and decreased nNOS protein expression occur while purinergic transmission is unaffected. These findings indicate that nitrergic enteric neuropathy may be a primary dysfunction in diabetes, independent from vagal dysfunction.

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“…Consequently, impairment of NO synthesis and bioavailability affects NO-cGMP pathway and thereby neurogenic and endothelium-dependent relaxation of smooth muscle in CC is also impaired (Levine et al, 1990;Azadzoi & Saenz de Tejada, 1992). Moreover, experimental diabetic rats showed impaired endothelium-dependent relaxation of aorta (Rosen et al, 1990) and decreased intracavernous pressure (ICP) response by electrostimulation (Way & Reid, 1994;Mcvary et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Chronic administration of phosphodiesterase 5 inhibitor improves erectile and endothelial function in a rat model of diabetes

Ahn

Choi

et al. 2005

Int J of Andrology

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This study was conducted to determine if the long-term administration of the phosphodiesterase type 5 (PDE 5) inhibitor, DA-8159, to diabetic rats can ameliorate the development of erectile dysfunction (ED) and endothelial dysfunction. After inducing diabetes with streptozotocin, DA-8159 was orally administered at a dose of 3 mg/kg or 10 mg/kg for 8 weeks. To examine the effect on erectile response, electrostimulation of the cavernous nerve with the parameters of 3 V, 5 ms, 5 Hz or 10 Hz, was performed to measure the intracavernous pressure (ICP) and mean arterial pressure (MAP). Thoracic aorta relaxation in vitro was evaluated by adding acetylcholine (Ach) cumulatively to the bathing medium. In addition, the plasma endothelin-1 (ET-1) levels were measured in order to investigate the effect of DA-8159 on endothelial dysfunction. The area under the curve (AUC) from the ICP/MAP ratio in the 10 Hz stimulation showed a significantly increased AUC after the 10 mg/kg treatment compared with the diabetic group (8891 +/- 619 vs. 6316 +/- 1016, respectively, p < 0.05). At the 5 Hz frequency, DA-8159 10 mg/kg also induced a significant increase in the AUC compared with the diabetic control. The maximum ICP/MAP ratio (%) of the 10 mg/kg treatment group was significantly higher in both the 10 Hz and 5 Hz frequency groups (p < 0.05). A treatment of 3 mg/kg tended to increase the AUC and peak ICP/MAP but was not statistically significant. The Ach EC50 value of the diabetic group was significantly higher than in the normal control (120.50 +/- 22.90 nm vs. 86.80 +/- 9.30 nm, respectively), and 10 mg/kg treatment group showed a significantly lower EC(50) value (88.38 +/- 19.7 nm). The ET-1 level was lower in groups treated with DA-8159, 3 mg/kg and 10 mg/kg treatment induced a statistical difference compared with the diabetic control (1.15 +/- 0.34 fmol/mL vs. 2.51 +/- 0.55 fmol/mL, respectively, p < 0.05). These results demonstrate that chronic administration of DA-8159 could attenuate the development of the ED in diabetes and its effect is associated with an improvement in the endothelial function.

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Nitric oxide-mediated neurotransmission is attenuated in the anococcygeus muscle from diabetic rats

Cited by 5 publications

References 19 publications

Impairment of nitrergic‐mediated relaxation of rat isolated duodenum by experimental diabetes

Impairment of nitrergic‐mediated relaxation of rat isolated duodenum by experimental diabetes

Characterization of myenteric neuropathy in the jejunum of spontaneously diabetic BB‐rats

Chronic administration of phosphodiesterase 5 inhibitor improves erectile and endothelial function in a rat model of diabetes

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