Acute pancreatitis (AP) is an inflammatory disease characterized by tissue
edema,
necrosis and
hemorrhage. The mortality rate associated with this disease is particularly high when the
inflammation has become systemic. Recently, activation of the pancreatic renin-angiotensin system (RAS) was shown to play a role in AP. The present study investigated whether administering an AT1 receptor antagonist decreases the severity of AP and
pancreatitis-induced systemic
inflammation, particularly
pulmonary injury. Rats with AP-associated
lung injury were induced by multiple doses of
caerulein, which was demonstrated in the previous studies. Three
injections of
losartan (200 microg/ kg/h) were given 30 min prior to the first injection of
caerulein. The results demonstrated that
caerulein injections resulted in significant increases in pancreatic and pulmonary
myeloperoxidase (MPO) activities, and
losartan treatment attenuates these effects. Lung microvascular permeability was also significantly improved by
losartan treatment.
Losartan prevented
caerulein-induced pancreatic and pulmonary morphological alterations, but not elevations in serum
alpha-amylase or pancreas/
body weight ratio. These data indicate that
losartan treatment can attenuate pancreatic and
lung injury. Thus, the implication is that a blockade of AT1 receptors may have a clinical application for the treatment of AP and, perhaps more importantly, subsequent pulmonary complications.