Neuronal Nitric Oxide Mediates the Anti-inflammatory Effects of Intestinal Ischemic Preconditioning

Abstract

Background: Ischemic preconditioning (IPC) can provide a defense against ischemiaereperfusion (IR)-induced acute inflammation and barrier dysfunction in many organs. Because nitric oxide (NO) has been implicated as a trigger or mediator in the IPC mechanism and because neuronal NO synthase (nNOS) is a dominant isoform of NOS in the gastrointestinal tract, our aim was to investigate the role of nNOS in IPC-induced protection after mesenteric IR. Materials and methods: Intestinal IR was induced in sodium pentobarbitaleanesthetized dogs by clamping the superior mesenteric artery for 60 min followed by 2 h of reperfusion (IR group; n ¼ 7). In further groups, IPC was used (three cycles of 5-min ischemia/5-min reperfusion periods) before IR in the presence or absence of selective inhibition of nNOS with 7-nitroindazole (5 mg/kg, intravenously, in a bolus 15 min before IPC, n ¼ 6 each). Changes in mesenteric vascular resistance, intramucosal pH (pHi), and small bowel motility were monitored. Plasma nitrite/nitrate levels, intestinal NO synthase activity, leukocyte accumulation, mast cell degranulation, and histologic injury were also determined. Results: Ischemia significantly decreased mesenteric vascular resistance and pHi, whereas IR induced a temporary bowel hypermotility and acute inflammatory reaction. IPC facilitated pHi recovery, attenuated motility dysfunction, elevated NOS-dependent NO production, and reduced leukocyte accumulation, mast cell degranulation, and mucosal injury. Pretreatment with 7-nitroindazole halted the IPC-induced increase in NO availability, pHi recovery, and the anti-inflammatory and morphologic effects. Conclusions: Our data demonstrate that NO generated by intestinal nNOS plays a pivotal role in IPC-linked tissue protection by inhibiting an IR-related acute inflammatory response.

MitoQ Modulates Lipopolysaccharide-Induced Intestinal Barrier Dysfunction via Regulating Nrf2 Signaling

“…Nitric oxide was suggested to regulate inflammatory response during sepsis [23]. Enhanced production of nitric oxide is associated with the intestinal barrier injury during inflammation [24]. The inhibition of nitric oxide secretion significantly protect against tissue injuries during sepsis [23].…”

Insights into the effects of inducible and neuronal nitric oxide synthase isoenzymes in experimental intestinal heterophyiasis

“…Such a difference in the concentration between both markers was statistically significant (Table 4, P<0.05). The selective inhibitory effect of 7-NI on the intestinal nNOS enzyme expression was also reported [52] . The researchers showed the antiinflammatory effect of nNOS isoenzyme on preserving the morphological intestinal integrity of experimentally ischaemic dogs when using 7-NI drug as a selective inhibitor of nNOS.…”

Adverse Effects of Bisphenol A on the Liver and Its Underlying Mechanisms: Evidence from In Vivo and In Vitro Studies

“…Nitric oxide (NO) is a signalling molecule that plays an important role in a wide range of physiological processes, including inflammatory responses. Under normal physiological circumstances, it has an anti-inflammatory influence [ 57 , 58 ]. NO, on the other hand, is a proinflammatory mediator that, in abnormal conditions, causes inflammation due to excessive production [ 59 , 60 ].…”