Microcirculatory disturbances are important early pathophysiological events in various organs during acute pancreatitis (AP). The aim of the study was to investigate an influence of L-arginine (nitric oxide substrate) and N(G)-nitro-L-arginine (L-NNA, nitric oxide synthase inhibitor) on organ microcirculation in experimental acute pancreatitis induced by four consecutive intraperitoneal cerulein injections (15 microg/kg/h). The microcirculation of pancreas, liver, kidney, stomach, colon and skeletal muscle was measured by laser Doppler flowmeter. Serum interleukin 6 and hematocrit levels were analyzed. AP resulted in a significant drop of microperfusion in all examined organ. L-arginine administration (2 x 100 mg/kg) improved the microcirculation in the pancreas, liver, kidney, colon and skeletal muscle, and lowered hematocrit levels. L-NNA treatment (2 x 25 mg/kg) caused aggravation of edematous AP to the necrotizing situation, and increased IL-6 and hematocrit levels. A further reduction of blood perfusion was noted in the stomach only. It is concluded that L-arginine administration has a positive influence on organ microcirculatory disturbances accompanying experimental cerulein-induced AP. NO inhibition aggravates the course of pancreatitis.
The aim of the study was to investigate the potential role of nitric oxide (NO) on the microcirculation in experimental acute pancreatitis in rats. Twenty-five rats were divided into the following groups: group A (5 rats) = control; group B (5 rats) = acute pancreatitis induced by retrograde taurocholate infusion into the pancreatobiliary duct without treatment; group C (5 rats) = acute pancreatitis treated with the NO donor L -arginine; group D (5 rats) = acute pancreatitis treated with the NO synthase inhibitor N-nitro- L -arginine (L-NNA); group E (5 rats) = without pancreatitis receiving L -NNA. The animals were observed throughout 4 h. The microcirculatory values of the pancreas, liver, colon, stomach and kidney were measured by means of laser Doppler flowmetry. Three animals of group D died after the third hour of the experiment. In rats with pancreatitis, a rapid decrease in microcirculatory values was observed. The most pronounced drop in capillary blood flow within all the organs was observed in rats treated with the NO synthase inhibitor L -NNA, L -arginine administration in rats with acute pancreatitis slightly improved the microcirculatory values, although the improvement was significant in colon perfusion only. We conclude that NO may have a beneficial influence on the capillary organ perfusion in acute pancreatitis. The administration of an NO synthase inhibitor seems to have a detrimental effect on acute pancreatitis.
The aim of this study was to investigate the impact of L-arginine (nitric oxide synthase substrate), L-NG-nitro-L-arginine (nitric oxide synthase inhibitor), and heparin on the pancreas microcirculation, serum IL-6 level and microscopic alterations of the pancreas in acute pancreatitis in rats. Acute pancreatitis was induced by 4 i.p. injections of cerulein (15mg/kg). Microcirculatory values were measured by means of laser Doppler flowmetry 5 h after the first cerulein injection. Remarkable histopathological changes in the pancreas, including parenchymal necrosis, an elevation of serum IL-6 level, and a significant drop of pancreatic capillary perfusion was observed in rats with nitric oxide synthase inhibition. L-arginine improved the pancreatic microcirculation but worsened the microscopic alterations within the pancreas. Heparin had a beneficial effect on the microcirculatory values, serum IL-6 concentration, and morphologic changes. Authors conclude that inhibition of nitric oxide synthase aggravates acute pancreatitis. L-arginine treatment improves pancreatic perfusion but potentiates morphological alterations. Heparin, improving the microcirculation and inflammatory changes within the pancreatic gland, may be considered as a promising therapeutic agent in acute pancreatitis.
