Involvement of endogenous nitric oxide in the regulation of rat intestinal motility in vivo

doi:10.1016/0014-2999(92)90567-N

European Journal of Pharmacology

Volume 229, Issues 2–3, 15 December 1992, Pages 273-276

https://doi.org/10.1016/0014-2999(92)90567-N Get rights and content

Abstract

The effect of the nitric oxide (NO) synthase inhibitor, N^G-nitro-L-arginine methyl ester (L-NAME) on the motility of the small intestine in an acute model in the anaesthetised rat was determined by changes in jejunal intraluminal pressure. L-NAME (0.5–10 mg kg⁻¹ i.v.) caused a dose-dependent increase in intraluminal pressure and initiated phasic intestinal contractions. These responses were inhibited by concurrent administration of L-arginine (200 mg kg⁻¹ i.v.) but not by D-arginine (200 mg kg⁻¹). The increase in jejunal motility induced by L-NAME was attenuated by atropine (4 mg kg⁻¹), although even high doses of atropine (16 mg kg⁻¹) did not abolish these responses. This indicates that although there are interactions between NO and muscarinic cholinergic mechanisms, other processes are also involved in these contractile events following administration of L-NAME. These observations in the rat suggest that endogenous NO plays a role in the modulation of intestinal motility in vivo.

References (15)

G.E. Boeckxstaens et al.
Non-adrenergic noncholinergic relaxation mediated by nitric oxide in the canine ileocolonic junction
Eur. J. Pharmacol.
(1990)
L.E. Gustafsson et al.
Modulation of autonomic neuroeffector transmission by nitric oxide in guinea-pig ileum
Biochem. Biophys. Res. Commun.
(1990)
F. Hata et al.
Essential role of nitric oxide in descending inhibition in the rat proximal colon
Biochem. Biophys. Res. Comm.
(1990)
J.M. Pique et al.
The vasodilator role of endogenous nitric oxide in the rat gastric microcirculation
Eur. J. Pharmacol.
(1989)
N. Toda et al.
Role of nitric oxide in non-adrenergic, non-cholinergic nerve-mediated relaxation in dog duodenal longitudinal muscle strips
Jap. J. Pharmacol.
(1990)
H.-D. Allescher et al.
Nitric oxide as a putative nonadrenergic noncholinergic inhibitory transmitter in the canine pylorus in vivo
Am. J. Physiol.
(1992)
D.S. Bredt et al.
Localization of nitric oxide synthase indicating a neural role of nitric oxide
Nature
(1990)

There are more references available in the full text version of this article.

Cited by (110)

Increase of n-NOS and i-NOS in Rat Colon After Sacral Neuromodulation
2017, Neuromodulation
Citation Excerpt :
It has been demonstrated how the synthesis of NO can play a key role in intestinal motility. Calignano et al. demonstrated how the administration of the NO synthase inhibitor, L-NAME, correlates with an increased intestinal motility, defined as increased intraluminal jejunal pressure and small bowel peristaltic contractions, in an in vivo rat model (24). Different studies demonstrated the implication of NO in small bowel motility both in rats and humans (25,26).
Sacral neuromodulation (SNM) is proposed to treat different anorectal dysfunctions but its mechanism of action is not yet known. Our previous study demonstrated how SNM can significantly increase neuronal nitric oxide synthase NOS (n-NOS) and inducible NOS (i-NOS) expression in the anus and rectum of rats. There are no reports regarding the relation between SNM and NOS in colonic cells: our aim was to assess NOS expression in colonic rat model after SNM.
Twenty-six female Sprangue-Dawley rats were considered: group I, normal control rats; group II, sham treatment rats, in whom electrodes for electrical stimulation were placed in S1 foramen bilaterally and left in place, without performing neuromodulation; group III, rats in whom SNM was performed. After 14 days, the rats were sacrificed and we evaluated n-NOS and i-NOS in colonic specimens by immunohistochemistry and Western Blot analysis.
Western Blot analysis showed that levels of n-NOS and i-NOS were higher in colon of the III group rats respect to the others; in particular, immunohistochemistry revealed that, after neuromodulation, n-NOS expression in the muscle cells and i-NOS expression in glandular epithelium and nervous cells were highly represented (p < 0.05).
Our study showed that in colon, SNM is able to influence NO synthesis, activating n-NOS expression in muscle cells and i-NOS expression in glandular epithelium and nervous cells. Our study showed a complex colonic response to SNM. This experimental model could be applied to better understand the mechanism of action of SNM in bowel dysfunction.
In vitro smooth muscle contractility before and after relief of experimental obstruction in the rat: Application to the surgical management of ileal dilatation
2014, Journal of Pediatric Surgery
Bowel dilatation occurs proximal to an obstruction and predisposes to intestinal dysmotility. The present study sought to determine whether or not changes in smooth muscle contractility and the thickness of the proximal, dilated bowel wall can be reversed following relief of the obstruction.
Three groups of seven male Wistar rats were studied. In 8-week-old animals in a control group and a sham-operated group, a small segment of bowel (designated as R1 for controls and R2 for shams) was resected 5.0 cm from the cecum. In the third (operated) group, a narrow, isoperistaltic intestinal loop was created proximal to an end-to-end anastomosis of the ileum in 4-week-old animals. When these animals were 6 weeks old, the loop was re-anastomosed to the distal small bowel (after resection of the loop's distal portion, referred to as R3). Two weeks later, a small segment of bowel was resected proximal to the anastomosis (R4). We evaluated the thickness of the smooth muscle layers and the in vitro contractile responses of circular smooth muscle ileal strips (R1–R4) to electrical stimulation and pharmacological stimulation (with KCl, acetylcholine (ACh), substance P, N^G-nitro-l-arginine methyl ester (L-NAME) and histamine).
The amplitudes of contraction in response to electrical and Ach-mediated stimulation were higher for R3 than for R4 (P < 0.001), R1 and R2 (both P < 0.05). Compared with R1 and R2, the smooth muscle layer was three times as thick in R3 (P < 0.001) and 2.5 times as thick in R4 (P < 0.01).
Our study provides evidence of the possible recovery of intestinal motility (in response to neurotransmitters involved in gut function) after the relief of an obstruction. If ileal motility can conceivably return to normal values, conservative surgical procedures in pediatric patients should be preferred (in order to leave a sufficient length of bowel and avoid short bowel syndrome).
Nitric oxide-sensitive guanylyl cyclase is dispensable for nitrergic signaling and gut motility in mouse intestinal smooth muscle
2011, Gastroenterology
The nitric oxide–guanosine 3',5'-cyclic monophosphate (cGMP) signaling pathway has an important role in the control of smooth muscle tone. NO is produced by NO synthases and acts as a major inhibitory neurotransmitter in the gastrointestinal (GI) tract. The main target, NO-sensitive guanylyl cyclase (NO-GC), is stimulated by NO to produce the intracellular messenger cGMP. We investigated the role of NO-GC in nitrergic relaxation and GI motility.
We tested relaxation of GI smooth muscle in mice that do not express NO-GC or mice with disruption of NO-GC specifically in smooth muscle cells. Different segments of the GI tract (fundus, lower esophageal sphincter, pyloric sphincter, and duodenum) were used in isometric force studies. NO donors and electrical field stimulation were used to assess nitrergic signaling. Whole-gut transit time was measured as an indicator of GI motility.
Mice that lack NO-GC do not have NO-induced relaxation of GI smooth muscle. Gut transit time was increased, resulting in GI dysfunction. Surprisingly, in mice that lack NO-GC specifically in smooth muscle, NO-induced relaxation was reduced only slightly, and whole-gut transit time was unchanged compared with wild-type mice.
Lack of NO-GC in smooth muscle cells does not impair NO-induced relaxation of GI tissues or GI motility. The NO receptor guanylyl cyclase in GI smooth muscle is therefore dispensable for nitrergic signaling in mice.
Alterations in spontaneous contractions of rat ileum and jejunum after peritonitis
2008, European Journal of Pharmacology
The aim of this study was to investigate the effects of peritonitis on spontaneous contractions of ileum and jejunum smooth muscles isolated from rats. Peritonitis was induced by cecal ligation and puncture in 8 rats. Another group of 8 rats underwent a sham operation and acted as controls. Twenty-four hours after the operation, the rats were killed, and their ileum and jejunum smooth muscles were excised and placed in circular muscle direction in a 10 ml organ bath. Changes in the amplitude and frequency of spontaneous contractions were analyzed before and after the addition of different antagonists. Peritonitis induced the decrease in the amplitude and frequency of spontaneous contractions in ileum and jejunum smooth muscles. In control groups, both ileum and jejunum, the amplitude and frequency of spontaneous contractions were significantly elevated in the presence of N^G-nitro-l-arginine (l-NNA) and indomethacin. In peritonitis groups, both ileum and jejunum, the amplitude and frequency of spontaneous contractions were significantly enhanced in the presence of l-NNA, aminoguanidine, indomethacin and celecoxib compared to control values. In conclusion, peritonitis induces the decrease in the amplitude and frequency of spontaneous contractions of ileum and jejunum that can be attributed to the rise of nitric oxide synthase and cyclooxygenase isoforms levels.
Relationship of Environmental Nitrogen Metabolism to Human Health
2008, Nitrogen in the Environment
This chapter discusses sources and forms of nitrogen in the diet, human requirements for nitrogen, metabolism, and potential harmful and/or beneficial effects of certain forms of nitrogen and nitrogen metabolites in the body on human health. The need by humans to produce and consume food and other agricultural products is increasing with a growing population leading to increased human demands for nitrogen to produce food and other products. Therefore it is important to consider the impact of human intake, metabolism, and excretion of nitrogen-containing compounds will have on both humans and the environment. Protein was shown to be an essential source of nitrogen for humans. Other nitrogen-containing compounds were shown to impact human health as well, in both potentially deleterious and beneficial ways. Therefore it is important to continue to analyze and recognize the impact that nitrogen-containing compounds have on humans and the impact that will occur on the environment as the human population continues to grow.
Alterations in spontaneous contractions of rat proximal and distal colon after peritonitis
2007, Journal of Pediatric Surgery
The aim of this study was to investigate the effect of peritonitis on spontaneous contractions of distal and proximal colon smooth muscle isolated from rats.
Peritonitis was induced by cecal ligation and puncture in 8 rats. Another group of 8 rats underwent a sham operation and acted as controls. Twenty-four hours after the operation, the rats were killed; and their distal and proximal colon smooth muscle was excised and placed in circular muscle direction in a 10-mL organ bath. Changes in the amplitude and frequency of contractions were analyzed before and after the addition of antagonists.
Peritonitis induced the increase in the amplitude and frequency of spontaneous contractions. In both distal and proximal colon of the control group, the amplitude of spontaneous contractions was elevated by N^G-nitro-l-arginine and tetradotoxin; but the frequency of spontaneous contractions was significantly elevated only in the presence of N^G-nitro-l-arginine. In both distal and proximal colon of the peritonitis group, the enhanced amplitude and frequency were significantly decreased and returned to control values in the presence of celecoxib.
Peritonitis induces the increase in the amplitude and frequency of spontaneous contractions of distal and proximal colon, which can be attributed to a loss of inhibitor nitrergic and other neural control or rise of cyclooxygenase-2 levels.

View all citing articles on Scopus

View full text

Short communicationInvolvement of endogenous nitric oxide in the regulation of rat intestinal motility in vivo

Abstract

Eur. J. Pharmacol.

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Comm.

Eur. J. Pharmacol.

Jap. J. Pharmacol.

Nitric oxide as a putative nonadrenergic noncholinergic inhibitory transmitter in the canine pylorus in vivo

Am. J. Physiol.

Localization of nitric oxide synthase indicating a neural role of nitric oxide

Nature

Short communication
Involvement of endogenous nitric oxide in the regulation of rat intestinal motility in vivo