saralasin and Edema

Acute pancreatitis is an inflammatory disease characterized by pancreatic tissue edema, acinar cell necrosis, hemorrhage and inflammation of the damaged gland. It is believed that acinar cell injury is initiated by the activation of digestive zymogens inside the acinar cells, leading finally to the autodigestion of the pancreas. Previous study in our laboratory demonstrated that cerulein-induced acute pancreatitis was associated with an up-regulation of local renin-angiotensin system (RAS) in rat pancreas. Therefore, the utilization of RAS inhibitors may provide a novel and alternative treatment for acute pancreatitis. By means of a rat model of cerulein-induced acute pancreatitis, results from the present study showed that an intravenous injection of saralasin, an antagonist for angiotensin II receptors, at a dose of 40 microg/kg 30 min before the induction of acute pancreatitis significantly attenuated pancreatic edema. Results from the biochemical measurements showed that pretreatment with saralasin at a dose of 20 microg/kg markedly reduced pancreatic injury, as evidenced by the decreased activities of alpha-amylase and lipase in plasma. However, the same recipe of ramiprilat, a specific inhibitor for angiotensin-converting enzyme, at a dose of 20 microg/kg did not provide any protective effect against acute pancreatitis. On the contrary, pretreatment with ramiprilat at a dose 40 microg/kg enhanced cerulein-induced pancreatic injury. Results from histopathological analysis of these RAS inhibitors further confirmed with those results as obtained from biochemical analysis. These data indicate that administration of saralasin but not ramiprilat could be protective against acute pancreatitis and that activation of pancreatic RAS in acute pancreatitis may play a role in pancreatic tissue injury.

Topics: Acute Disease; alpha-Amylases; Angiotensin Receptor Antagonists; Animals; Ceruletide; Disease Models, Animal; Edema; Injections, Intravenous; Lipase; Necrosis; Pancreatitis; Ramipril; Rats; Rats, Sprague-Dawley; Renin-Angiotensin System; Saralasin

The mechanism(s) of the waning of the vasodilation and increase in vascular permeability during prolonged local intraarterial infusions of bradykinin (BK) was investigated in this study. Treatment with phentolamine or saralasin failed to prevent the waning of the vasodilation during the prolonged infusion of BK into forelimbs perfused at constant flow. In contrast, BK produced a sustained vasodilator response after treatment with captopril. Forelimb weight and lymph analysis were used to quantitate edema formation and to determine the duration of the increase in vascular permeability during prolonged local intra-arterial infusions of BK into forelimbs perfused at constant flow. The lymph-to-plasma ratios (L/P) for protein and FITC-Dextrans (fluorescein isothiocyanate dextrans, 70,000 Da) were determined, and clearances for protein and FITC-D were calculated. BK markedly increased fluid filtration, the protein L/P, and protein clearance resulting in edema formation. The protein L/P remained markedly elevated throughout the experimental period. The FITC-D L/P was markedly increased in the groups of animals in which the tracer was injected intravenously at the start or 8 min after the start of the prolonged BK infusion. In the groups of animals in which the tracer was injected intravenously 15-60 min after the start of the prolonged BK infusion, the FITC-D L/P failed to exceed the FITC-D L/P in control animals, although the protein L/P remained elevated. Pretreatment with both captopril and propranolol dramatically potentiated the magnitude of the increase in protein clearance, the filtration rate, and edema formation produced by BK but failed to affect the duration of the transient increase in vascular permeability.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Bradykinin; Captopril; Dogs; Edema; Female; Lymph; Male; Peptidyl-Dipeptidase A; Phentolamine; Propranolol; Reference Values; Saralasin; Vasodilation

Topics: Adrenal Glands; Aldosterone; Angiotensin II; Animals; Ascites; Blood Pressure; Corticosterone; Edema; Male; Natriuresis; Potassium; Rabbits; Regional Blood Flow; Renin; Saralasin; Time Factors; Vena Cava, Inferior

1. In the dog constriction of the thoracic region of the inferior vena cava increases water intake and extracellular and plasma fluid volumes. 2. Restriction of water intake to the pre-operative level for 2 weeks reduces the measured extracellular fluid volume to the pre-operative level. 3. Administration of the competitive angiotensin inhibitor, saralasin acetate, to two dogs in congestive cardiac failure following thoracic caval constriction markedly reduced their water intake. 4. These results suggest that increased fluid intake is probably important in the aetiology of the oedema associated with congestive cardiac failure, probably through the renin-angiotensin system.

Topics: Angiotensin II; Animals; Blood Proteins; Dogs; Edema; Extracellular Space; Female; Heart Failure; Hematocrit; Ligation; Male; Osmolar Concentration; Plasma Volume; Potassium; Saralasin; Sodium; Thirst; Vena Cava, Inferior; Water Deprivation