A crucial role of nitric oxide in acute lung injury secondary to the acute necrotizing pancreatitis

Abstract

<jats:p> To investigate the role of nitric oxide (NO) in acute lung inflammation and injury secondary to acute necrotizing pancreatitis (ANP), 5% sodium taurocholate was retrogradely injected into the biliopancreatic duct of rats to ANP model. These ANP rats were given L-Arginine (L-Arg, 100 mg/kg), L-NAME (10 mg/kg), or their combination by intraperitoneal injection 30 min prior to ANP induction. At 1, 3, 6, and 12 hours after ANP induction, lung NO production, and inducible NO synthase (iNOS) expression were measured. Lung histopathological changes, bronchoalveolar lavage (BAL) protein concentration, proinflammatory mediators tumor necrotic factor alpha (TNF-α), and lung tissue myeloperoxidase (MPO) activity were examined. Results showed that NO production and iNOS mRNA expression in alveolar macrophages (AMs) were significantly increased along with significant increases in lung histological abnormalities and BAL proteins in the ANP group, all of which were further enhanced by pretreatment with L-Arg and attenuated by pretreatment with L-NAME, respectively. These markers were slightly attenuated by pretreatment with combination of L-Arg + L-NAME, suggesting that NO is required for initiating the acute lung damage in ANP rats, and also that L-Arg-enhanced lung injury is mediated by its NO generation rather than its direct effect. MPO activity and TNF-α expression in lung were upregulated in the ANP rats and further enhanced by pretreatment with L-Arg and attenuated by pretreatment with L-NAME, respectively. These results suggest that overproduction of NO mediated by iNOS in the lung is required for the acute lung inflammation and damage secondary to ANP. </jats:p>

Pancreatic ascites hemoglobin contributes to the systemic response in acute pancreatitis

“…One of the mechanisms that may contribute to pulmonary hypertension is the increase in isoprostane levels that we report here, because F 2 -isoprostanes are powerful constrictors in human pulmonary smooth muscle [42] and cause pulmonary vasoconstriction and hypertension in the rat lung [43,44]. Furthermore, extracellular Hb strongly upregulated inos in the lung, which would certainly contribute to the acute lung inflammation and damage associated with necrotizing pancreatitis as previously reported [45].…”

Honokiol Attenuates the Severity of Acute Pancreatitis and Associated Lung Injury via Acceleration of Acinar Cell Apoptosis

“…These early and late inflammatory responses partially account for unsuccessful therapies in severe acute pancreatitis (24). Nitric oxide has also been implicated in the development of acute pancreatitis (26,27). Acute lung injury is the most common extrapancreatic complication of acute pancreatitis.…”

The Effect of N^G-Nitro-<i>L</i>-Arginine Methyl Ester, a Nitric Oxide Synthase Inhibitor, on Respiratory Mechanics in Rats

“…Intraperitoneal administration of L -NAME is a well-documented procedure [38,39,40], and the dosage utilized here was chosen based on previously published results to obtain a significant inhibition of NOS activity [38,39,40,41]. In particular, Cheng et al [39] demonstrated significantly attenuated NO production and NOS mRNA expression in rats treated with 10 mg/kg i.p.…”

“…In particular, Cheng et al [39] demonstrated significantly attenuated NO production and NOS mRNA expression in rats treated with 10 mg/kg i.p. L -NAME, a lower dosage than the one used in this study.…”