Vasoactive drugs, microvascular permeability, and hemorrhagic pancreatitis in cats.
We investigated the mechanisms by which 16,16-dimethyl prostaglandin E2 and histamine induced pancreatic hemorrhage in an experimental model of acute pancreatitis in cats. In normal animals, when large molecular weight dextran molecules were infused into the systematic circulation, they were recovered in secretin-stimulated pancreatic juice in low concentrations. Both 16,16-dimethyl prostaglandin E2 (in a dose that increased splenic artery blood flow and microvascular permeability) and histamine (in a dose that increased permeability only) increased the amount of dextran recovered in pancreatic juice. Isoproterenol, in a dose that produced the same increase in blood flow as 16,16-dimethyl prostaglandin E2 but which did not increase microvascular permeability, did not alter the amount of dextran recovered. This suggested that the increase in dextran output after 16,16-dimethyl prostaglandin E2 was primarily due to the increase in microvascular permeability caused by the drug. In other experiments, a combination of H1- and H2-receptor antagonists (mepyramine and cimetidine) protected against the development of pancreatic hemorrhage in both the prostaglandin- and histamine-treated animals. Indomethacin (a cyclooxygenase inhibitor) protected against the development of hemorrhage in the histamine-treated animals. Our results support the hypothesis that changes in microvascular permeability may be important in the pathogenesis of parenchymal hemorrhage in this model.
Harvey
M H
MH
Department of Surgery, University of Missouri Health Sciences Center, Columbia.
Wedgwood
K R
KR
Reber
H A
HA
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002415:Cats; D002927:Cimetidine / Q000627:therapeutic use; D004357:Drug Synergism; D005260:Female; D006470:Hemorrhage / Q000209:etiology* / Q000517:prevention & control; D006632:Histamine / Q000633:toxicity*; D007213:Indomethacin / Q000627:therapeutic use; D008297:Male; D010195:Pancreatitis / Q000209:etiology* / Q000517:prevention & control; D011459:Prostaglandins E, Synthetic / Q000633:toxicity*; D011738:Pyrilamine / Q000627:therapeutic use
D011459:Prostaglandins E, Synthetic; C017244:16,16-dimethylprostaglandin E; D002927:Cimetidine; D006632:Histamine; D011738:Pyrilamine; D007213:Indomethacin