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Contrasting effects of circulating nitric oxide and nitrergictransmission on exocrine pancreatic secretion in rats |
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| Authors: | E Vaquero X Molero V Puig-Divi J Malagelada |
| Affiliation: | Digestive System Research Unit, Hospital General Universitari Vall d''Hebron, Barcelona, Spain. |
| Abstract: | Background—Nitric oxide (NO) blockade byL-nitroarginine methyl ester (L-NAME) inhibitspancreatic secretion in vivo and aggravates caerulein inducedpancreatitis. Nitric oxide synthase (NOS) is present in pancreaticislets, endothelium, and nerve fibres. L-NAME blocks allknown NOS isoforms. Aim—To investigate the source of NO blocked byL-NAME that inhibits amylase secretion. Methods—Amylase output was measured in rats inresponse to caerulein (0.1-50 µg/kg) alone or with indazole.Baseline secretion and the response to supramaximal caerulein were alsoexamined after administration of indazole, L-NAME,haemoglobin, or aminoguanidine under continuous blood pressuremeasurement. In separate experiments, pancreatic secretion was measuredafter blockade of afferent nerve fibres by either systemic or localcapsaicin. The effect of neural NOS inhibition on caerulein inducedpancreatitis was also investigated. Results—L-NAME, haemoglobin, andsupramaximal caerulein (10 µg/kg) increased blood pressure, whereasindazole and suboptimal caerulein (0.1 µg/kg) did not. Indazole andcapsaicin decreased basal amylase output. L-NAME andhaemoglobin reduced basal amylase output to a lesser extent andpotentiated the inhibitory response to supramaximal caerulein. Incontrast, full neural NOS inhibition by L-NAME partiallyreversed the expected caerulein induced suppression of amylase output.This effect was reproduced by indazole and capsaicin. Indazole did notalter responses to either optimal (0.25 µg/kg) or suboptimal (0.1 µg/kg) caerulein, nor, in contrast with L-NAME, aggravatethe outcome of caerulein induced pancreatitis. Conclusions—Reduction of circulating NOavailability, probably of endothelial origin, is responsible for thedecrease in amylase secretion observed in the early response toL-NAME. Nitrergic neurotransmission plays an important rolein the control of pancreatic secretion and may induce opposite effectsto endothelial NOS activity. |
| Keywords: | nitric oxide pancreatic secretion pancreatitis indazole haemoglobin |