Expression of nitric oxide synthase isoforms and nitric oxide production in acute pancreatitis and associated lung injury.
OBJECTIVE
The role of nitric oxide (NO) has been increasingly implicated in the pathophysiology of acute pancreatitis (AP). Studies have shown increased NO production in AP although not all are agreeable on whether NO is beneficial or detrimental in AP. This study aims to profile NO production and NO synthase (NOS) expression in the pancreas and lungs in the progression of AP in mice to gain insights to the role played by different NOS isoforms.


METHODS
AP was induced in mice by hourly administration of cerulein. NO production was determined by measuring the total nitrite and nitrate (NOx) content while NOS expression was measured by Western blot.


RESULTS
Pancreatic NO production increased sharply and was sustained throughout AP. iNOS expression was greatly increased while eNOS was downregulated at the later stages. In the lungs, there was an unexpected early increase in the constitutive NOS expression; however iNOS was also significantly overexpressed at the later time point along with a significant increase in NO. Acinar cells were found to overproduce NO in response to cerulein hyperstimulation with iNOS again being the major contributor.


CONCLUSIONS
These data show that NO production and NOS expression are differentially regulated temporally and in magnitude in the pancreas and lungs in response to cerulein hyperstimulation which suggests differing roles for each NOS isoform. and IAP.
Ang
Abel Damien
AD
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Adhikari
Sharmila
S
Ng
Siaw Wei
SW
Bhatia
Madhav
M
D000208:Acute Disease; D000818:Animals; D002108:Ceruletide; D008168:Lung / Q000201:enzymology; D055370:Lung Injury / Q000201:enzymology*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D010179:Pancreas / Q000201:enzymology; D010195:Pancreatitis / Q000139:chemically induced / Q000201:enzymology*
D009569:Nitric Oxide; D002108:Ceruletide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse