substance-p--arg(1)-pro(2)-trp(7)-(9)-leunh(2)(11)- and Acute-Disease

The present study was conducted to examine the contribution of substance P to the pancreatic microcirculatory dysfunction during acute pancreatitis.. Pancreatitis was elicited by up to 6 hourly injections of cerulein (50 microg/kg IP) in male C57Bl/6 mice. At 0, 1, 3, and 6 hours after cerulein treatment, the pancreatic microvasculature in anesthetized mice was studied using established high-resolution in vivo microscopic methods.. Treatment of mice with cerulein for 6 hours caused a 30% decrease in capillary perfusion and the diameter of the capillaries and an increase in microvascular permeability (20%) and interstitial space (30-fold). The administration of the substance P receptor antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11) (2 mg/kg IP) minimized the pancreatic microcirculatory dysfunction 3 hours after cerulein treatment. The superfusion of substance P for 0.5 hours decreased the diameter (by 22%) and increased microvascular permeability (by 23%) along with interstitial space (22-fold increase). Blockade of substance P receptor attenuated substance P-induced pancreatic microcirculatory dysfunction.. These results suggest that substance P mediates pancreatic microcirculatory dysfunction during the development of acute pancreatitis.

Topics: Acute Disease; Animals; Capillary Permeability; Ceruletide; Male; Mice; Mice, Inbred C57BL; Microcirculation; Microscopy, Video; Pancreas; Pancreatitis; Substance P