Expression of inducible nitric oxide synthase contributes to the development of pancreatitis following pancreatic ischaemia and reperfusion.
BACKGROUND
Inducible nitric oxide synthase (iNOS) activity is increased in experimentally induced acute pancreatitis. Increased expression of this isoform of nitric oxide synthase has been demonstrated in several organs subjected to ischaemia-reperfusion injury. The present experiment investigated the expression of iNOS and the effect of selective iNOS inhibition in pancreatic ischaemia-reperfusion.


METHODS
Wistar rats (n = 40) were randomly and equally assigned to four groups. Groups 2 and 4 underwent 60 min of total pancreatic ischaemia followed by 6 h of reperfusion (I-R). Groups 1 and 3 underwent sham operation. The selective iNOS inhibitor L-N(6)-(1-iminoethyl)-lysine (L-NIL) was administered to groups 3 and 4. Expression of iNOS was examined by immunohistochemistry. Other investigations included measurement of serum amylase activity and pancreatic wet : dry weight ratio, and histopathological examination.


RESULTS
Eight of ten rats in group 2 (I-R only) expressed iNOS but none of the ten animals in group 1 (sham laparotomy) did so. Group 4 (I-R + L-NIL) animals had significantly lower serum amylase levels and wet : dry weight ratios than those in group 2 (I-R only). Microscopic evidence of pancreatic injury was present only in rats in group 2 (I-R only).


CONCLUSIONS
Expression of iNOS during reperfusion following pancreatic ischaemia contributes significantly to the development of acute pancreatitis.
Ayub
K
K
Division of Surgery, Anaesthetics and Intensive Care, Imperial College School of Medicine, Hammersmith Hospital, London W12 0NN, UK.
Serracino-Inglott
F
F
Williamson
R C
RC
Mathie
R T
RT
D000208:Acute Disease; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D007150:Immunohistochemistry; D007511:Ischemia / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010179:Pancreas / Q000098:blood supply*; D010195:Pancreatitis / Q000201:enzymology* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion / Q000009:adverse effects*
D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat