Substance P mediates cerulein-induced pancreatic microcirculatory dysfunction in mice.
OBJECTIVE
The present study was conducted to examine the contribution of substance P to the pancreatic microcirculatory dysfunction during acute pancreatitis.


METHODS
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.


RESULTS
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.


CONCLUSIONS
These results suggest that substance P mediates pancreatic microcirculatory dysfunction during the development of acute pancreatitis.
Ito
Yoshiya
Y
Department of Cell Biology and Anatomy, University of Arizona, Tucson, AZ 85724-5044, USA.
Lugea
Aurelia
A
Pandol
Stephen J
SJ
McCuskey
Robert S
RS
D000208:Acute Disease; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D002108:Ceruletide; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000187:drug effects / Q000378:metabolism; D018715:Microscopy, Video; D010179:Pancreas / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology
D013373:Substance P; C038073:substance P, Arg(1)-Pro(2)-Trp(7),(9)-LeuNH(2)(11)-; D002108:Ceruletide