Features of the gastric periodic activity in conditions of NO-ergic system disbalance
AbstractNitric oxide is the main inhibitory mediator of the gastrointestinal smooth muscles’ relaxation which stimulates duodenal mucus and bicarbonate secretion. More recent studies have demonstrated that NO also protected the gastrointestinal tract by inhibiting gastric acid secretion. In this study we investigated gastric secretory and motor activity considering the NO imbalance condition. The experiments were carried out on male white laboratory rats (200–230 g). The control group was treated with 0.9% NaCl solution. The injections of NO donator (1.5 mg/kg of 0.1% (Sigma-Aldrich) sodium nitroprusside solution) were made in the second and the third groups during 6 and 12 days. The fourth and the fifth group were treated with NO synthesis inhibitor (40 mg/kg of 1% solution (Sigma-Aldrich) Nω-nitro-L-arginine) during 6 and 12 days respectively. Recording of gastric myoelectric activity (GMA) and gastric juice collection were carried out under anesthesia (ketamine, 110 mg/kg). Next, its volume, pH, glycoprotein and pepsin were measured. Within 6-days stimulation of NO excess decreased gastric juice volume by 47% and increased pH compared to control samples. Pepsin level increased by 62% and glycoprotein level decreased by 68% compared to the checkpoint. After 6 days of L-NNA injections we observed the increase of gastric juice secretion volume (78%) and pH level, however, pepsin concentration remained unchanged. Glycoprotein level increased by 21% compared to control samples. After 12 day NO synthesis inhibitor injections gastric secretion volume increased by 85%. Gastric juice pH level was 200% higher than the control value and exceeded gastric juice pH level (62%) in the third group. In addition, pepsin level tended to decrease when NO deficiency simulation was prolonged. Glycoprotein level decreased by 41% compared to control samples and by 51% compared to the third group. Pepsin level decreased after 12 day NO-inhibitor injections as gastric juice pH level increased. After 12 day Na-nitroprusside treatment, gastric myoelectric index decreased by 42% compared to the checkpoint. The type of contractions is typical to the I phase of the basic electrical rhythm (BER). Also, retrograde entrainment of duodenal rhythm took place. After 6 day L-NNA injections, GMA was the same as the period between II and III phase of BER. Late second and early third phases predominated, while the I phase wasn’t detected during the recording. In case of long-lasting disorder of NO-system, motor index value significantly differed from the control group samples and depended on the duration of NO-synthase blocking. On the 6th day of L-NNA treatment, the level of motor index increased 1.5 times. GMA phases could be identified only on the basis of motor index values. Stomach’s own rhythms disappeared and duodenogastric reflux resulted in domination of duodenal rhythms. After 12 day L-NNA injections, duration of the II and III phases increased while the I phase of gastric BER disappeared; gastric motor index decreased by 27%. After considering the results of the current investigation, it can be stated that NO system imbalance leads to desynchronization of gastric active phases and, perhaps, reassigns the influence of different compensatory-adaptive mechanisms. The longer is the L-NNA treatment, the more gastric functions are imbalanced and the stronger is the process of destruction.
Bentz, M., Zaouter, C., Shi, Q., Fahmi, H., Moldovan, F., Fernandes, J.C., Benderdour, M., 2012. Inhibition of inducible nitric oxide synthase prevents lipid peroxidation in osteoarthritic chondrocytes. J. Cell. Biochem. 113(7), 2256–2267. >> doi:10.1002/jcb.24096
Cavicchi, M., Whittle, B.J., 1999. Potentiation of cytokine induced iNOS expression in the human intestinal epithelial cell line, DLD-1, by cyclic AMP. Gut 45(3), 367–374. >> doi:10.1136/gut.45.3.367
Currò, D., Preziosi, P. 1998. Non-adrenergic non-cholinergic relaxation of the rat stomach. Gen. Pharmacol. 31(5), 697–703. >> doi:10.1016/S0306-3623(98)00096-2
Elliott, S.N., Wallace, J.L., 1998. Nitric oxide: A regulator of mucosal defense and injury. J. Gastroenterol. 33(6), 792–803. >> doi:10.1007/s005350050178
Ivashkin, V.T., Drapkina, O.M., 2011. Klinicheskoe znachenie oksida azota i belkov teplovogo shoka [The clinical significance of nitric oxide and heat shock proteins]. Moscow (in Russian).
Jesedov, J.M., Magomedjeminova, A.S., 2010. Soderzhanie oksida azota v zheludochnom soke v zavisimosti ot kislotnosti zheludochnoj sekrecii u bol'nyh s zabolevanijami verhnego otdela pishhevaritel'nogo trakta [Gastric juice levels of nitric oxide in relation to gastric acidicity in patients with upper digestive tract diseases]. Klinicheskaja Laboratornaja Diagnostika 7, 48–50 (in Russian).
Kamata, K., Kohzuki, M., Misawa, M., Kasuya, Y., 1993.
Involvement of nitric oxide pathway in non-adrenergic non-cholinergic (NANC) relaxation in the rat stomach: Differential innervation of nanc nerves in the longitudinal and circular muscle of the fundus. Gen. Pharmacol. 24(6), 1403–1410. >> doi:10.1016/0306-3623(93)90426-X
Khattab, M.M., Gad, M.Z., Abdallah, D., 2001. Protective role of nitric oxide in indomethacin-induced gastric ulceration by a mechanism independent of gastric acid secretion. Pharmacol. Res. 43(5), 463–467. >> doi:10.1006/phrs.2001.0801
Kmonickova, E., Kverka, M., Tlaskalová-Hogenová, H., Kostecka, P., Zidek, Z., 2012. Stimulation of nitric oxide, cytokine and prostaglandin production by low-molecular weight fractions of probiotic Lactobacillus casei lysate. Neuro Endocrinol. Lett. 33(3), 166–172.
Kochar, N.I., Chandewal, A.V., Bakal, R.L., Kochar, P.N., 2011. Nitric oxide and the gastrointestinal tract. Int. J. Pharm. 7(1), 31–39. >> doi:10.3923/ijp.2011.31.39
Kovalyov, I.V., Baskakov, M.B., Kapilevich, L.V., Medvedev, M.A., 2004. Rol' oksida azota v reguljacii jelektricheskoj i sokratitel'noj aktivnosti gladkih myshc [Role of nitric oxide in the regulation of electrical and contractive activity of unstriped muscles]. Bull. Sib. Med. 1(1), 7–26 (in Russian).
Lamarque, D., Whittle, B.J., 1996. Involvement of peroxynitrite in the lipid peroxidation induced by nitric oxide in rat gastric mucosa. Eur. J. Pharmacol. 313(1), 5–7. >> doi:10.1016/0016-5085(95)23236-2
Mayev, I.V., Trukhmanov, A.S., Cheremushkina, N.V., 2008. Nitric oxide and its role in pathogenesis of gastroesophageal reflux disease. The Russian Medical Vesti 8(2), 3–9.
Mungrue, I.N., Gros, R., You, X., Pirani, A., Azad, A., Csont, T., Schulz, R., Butany, J., Stewart, D.J., Husain, M., 2002. Cardiomyocyte overexpression of iNOS in mice results in peroxynitrite generation, heart block, and sudden death. J. Clin. Invest. 109(6), 735–743. >> doi:10.1172/JCI0213265
Pacher, P., Beckman, J.S., Liaudet, L., 2007. Nitric oxide and peroxynitrite in health and disease. Physiol. Rev. 87(1), 315–424. >> doi:10.1152/physrev.00029.2006
Petrin, A., Sjebin, K., 2003. Nagljadnaja statistika v medicine [Visual statistics in medicine]. Geotar-Med, Moscow (in Russian).
Pokrovskij, V.I., 1997. Biomedicinskaja jetika [Biomedical ethics]. Medicina, Moscow (in Russian).
Polenov, S.A., 1998. Okis' azota v reguljacii funkcij zheludochno-kishechnogo trakta [Nitric oxide in the regulation of the gastrointestinal tract]. Rossijskij Zhurnal Gastrojenterologii, Gepatologii, Koloproktologii 1, 53–60 (in Russian).
Polotnjuk, S.Y., Shtanova, L.Y., Shtanova, T.V., Beregova, T.V., 2003. Doslіdzhennja rolі prostaglandinіv u reguljacіi oksidom azotu kisloto-sekretornoji funkcіji shlunka u shhurіv [Investigation of the role of prostaglandins in the regulation of nitrogen oxide acid-secretory function of the stomach in rats]. Ukrains'kі Medichnі Vіstі 5(1), 97 (in Ukranian).
Price, K.J., Hanson, P.J., Whittle, B.J., 1996. Localization of constitutive isoforms of nitric oxide synthase in the gastric glandular mucosa of the rat. Cell Tissue Res. 285(1), 157–163. >> doi:10.1007/s004410050631
Razuvaeva, O.V., Murzin, O.B., Rudenko, A.I., 2009. Dijal''nist' sekretornyh zaloz shlunka ta nitrergichni mehanizmy i'i' reguljacii' za umov modeljuvannja adrenalinovoi' vyrazky [Activity of stomach secretory glands and the nitrergic mechanisms of their regulatiоn under the condition of the adrenalin ulcer simulation]. Vìsn. Dnìpropetr. Unìv. Ser. Bìol. Ekol. 17(1), 193–198 (in Ukranian).
Rudenko, A.І., 2007. Motorna dijal'nist' gastroduodenal'noi' zony pry duodenogastral'nomu refljuksi u shhuriv [Motor activity in gastroduodenal duodenogastric reflux in rats]. Gastroenter-ologija 38, 119–127 (in Ukranian).
Schuman, E.M., Madison, D.V., 1993. Nitric oxide as an intercellular signal in long-term potentiation. Semin. Neurosci. 5(3), 207–215. >> doi:10.1016/S1044-5765(05)80054-5
Shapoval, L.N., Pobegailo, L.S., Stepanenko, L.G., Dmytrenko, O.V., Bouryi, V.A., Sagach, V.F., 2011. Impact of swimming exercise training on the effects of modulation of mitochondrial permeability transition and NOS-1 activation in medullary cardiovascular neurons of rats. Neurophysiology 43(4), 299–308. >> doi:10.1007/s11062-011-9230-4
Sharma, J.N., Al-Omran, A., Parvathy, S.S., 2007. Role of nitric oxide in inflammatory diseases. Inflammopharmacology 15(6), 252–259. >> doi:10.1007/s10787-007-0013-x
Stepanov, Y.M., Tverdokhleb, I.V., Sirenko, O.Y., 2012. Larginin: Svojstva, primenenie v medicine, toksichnost' i arginin-inducirovannoe porazhenie podzheludochnoj zhelezy [Larginine: Properties, application in medicine, toxicity, and arginine-induced acute pancreatitis]. Suchasna Gastroenterologija 65(3), 63–70 (in Ukranian).
Takeuchi, K., Araki, H., Kawauchi, S., Kunikata, T., Mizoguchi, H., Tashima, K., 2000. Regulatory mechanism of acid secretion in the damaged stomach: Role of endogenous nitric oxide. J. Gastroenterol. Hepatol. 15, 37–45. >> doi:10.1046/j.1440-1746.2000.02143.x
Tani, S., Itoh, H., Okabayashi, Y., Nakamura, T., Fujii, M., Fujisawa, T., Koide, M., Otsuki, M., 1990. New model of acute necrotizing pancreatitis induced by excessive doses of arginine in rats. Dig. Dis. Sci. 35(3), 367–374. >> doi:10.1007/BF01537416
van Griensven, M., Zeichen, J., Skutek, M., Barkhausen, T., Krettek, C., Bosch, U., 2003. Cyclic mechanical strain induces NO production in human patellar tendon fibroblasts – a possible role for remodelling and pathological transformation. Exp. Toxicol. Pathol. 54(4), 335–338. >> doi:10.1078/0940-2993-00268
Zvenigorodskaja, L.A., Nilova, T.V., 2008. Oksid azota kak marker vospalenija pri steatogepatite u bol'nyh s metabolicheskim sindromom [Nitric oxide as a marker of inflammation in steatohepatitis in patients with metabolic syndrome]. Bolezni Organov Pishhevarenija 10(2), 47–49 (in Russian).
Zvjagintseva, T.D., Gridneva, S.V., 2005. Vascular endothelium in norm and at gastrointestinal diseases. Contemporary Gastroenterology 22(2), 51–55.
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons «Attribution» 4.0 License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.