Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously demonstrated that therapy with a new specific endothelin-1 receptor antagonist (ET-RA) significantly reduced mortality in acute necrotizing pancreatitis (ANP) in the rat. Improved survival was not associated with decreased intrapancreatic trypsinogen activation or parenchymal necrosis but with reduced fluid sequestation into the third space suggesting that ET-RA counteracts systemic rather than local sequelae of severe pancreatitis. The present study further tests this hypothesis by evaluating the effect of the specific ET-1 antagonist LU-135252 on capillary blood flow, capillary density, and capillary permeability not only in the pancreas but also in the colon, and monitoring fluid losses and renal and respiratory function. The experiments demonstrate that therapy with the specific ET-RA started 6 hours after disease onset stabilizes increased capillary permeability in ANP not only in the pancreas but also in the colon. This is associated with reduced ascites and improved renal and respiratory function. Furthermore, ET-RA enhances decreased capillary blood flow and capillary density in the pancreas and colon. The present results are consistent with our previous observation that ET-RA improves outcome in ANP by counteracting systemic microcirculatory disorders (particularly capillary leakage) which are believed to contribute to organ failure in early pancreatitis in this model as well as in severe human pancreatitis.
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PMID:[Endothelin receptor block in acute pancreatitis--improvement of microcirculation and decrease of capillary permeability also distant from the pancreas]. 1451 90

The relative role of endothelin-1 receptors, ET(A) and ET(B) blockade in acute pancreatitis (AP) remains controversial. The aim of the study was to compare the effect of nonselective ET(A/B) antagonist (LU 302872) and selective ET(A)antagonist (LU 302146) in severe taurocholate AP in rats. Male Wistar rats with AP were treated with increasing doses: 1, 5 or 10 mg/kg b.w. of antagonists i.p. at 0, 6, 12, 18 h after induction of AP. In 24 h survivors, free active trypsin (FAT) and total potential trypsin (TPT), chymotrypsin and lipase in 12,000 x g supernatants of the pancreases were assayed. The index of trypsinogen activation (% FAT/TPT) was elevated in untreated AP to 29.2 +/- 5.0 vs 5.4 +/- 0.9 in the control (p < 0.001). ET(A/B) antagonist at increasing doses, diminished this index to 9.8 +/- 2.7, 10.3 +/- 1.6 and 10.1 +/- 2.0 respectively (p < 0.005). ET(A) antagonist reduced % FAT/TPT ratio to 10.6 +/- 1.9 (p < 0.005), 13.4 +/- 0.5 (p < 0.001) and 10.2 +/- 2.4 (p < 0.005) at respective doses. Both antagonists to a similar degree reduced the histological scores of inflammation, hemorrhages and necrosis. The increase in chymotrypsin and lipase activities after 24 h was not significant. In conclusion, both nonselective ET(A/B) and selective ET(A) antagonists attenuated to similar degree the augmented trypsinogen activation and pancreatic injury in taurocholate acute experimental pancreatitis in rats. Endothelin-1 receptor antagonists could be beneficial in the course of acute pancreatitis by the attenuation of trypsinogen activation.
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PMID:The effect of endothelin-1 receptor antagonists in acute experimental pancreatitis in the rats. 1462 May 34