Contrasting effects of circulating nitric oxide and nitrergic transmission on exocrine pancreatic secretion in rats

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Abstract

Background

Nitric oxide (NO) blockade by L-nitroarginine methyl ester (L-NAME) inhibits pancreatic secretion in vivo and aggravates caerulein induced pancreatitis. Nitric oxide synthase (NOS) is present in pancreatic islets, endothelium, and nerve fibres. L-NAME blocks all known NOS isoforms.

Aim

To investigate the source of NO blocked by L-NAME that inhibits amylase secretion.

Methods

Amylase output was measured in rats in response to caerulein (0.1-50 micro g/kg) alone or with indazole. Baseline secretion and the response to supramaximal caerulein were also examined after administration of indazole, L-NAME, haemoglobin, or aminoguanidine under continuous blood pressure measurement. In separate experiments, pancreatic secretion was measured after blockade of afferent nerve fibres by either systemic or local capsaicin. The effect of neural NOS inhibition on caerulein induced pancreatitis was also investigated.

Results

L-NAME, haemoglobin, and supramaximal caerulein (10 micro g/kg) increased blood pressure, whereas indazole and suboptimal caerulein (0.1 micro g/kg) did not. Indazole and capsaicin decreased basal amylase output. L-NAME and haemoglobin reduced basal amylase output to a lesser extent and potentiated the inhibitory response to supramaximal caerulein. In contrast, full neural NOS inhibition by L-NAME partially reversed the expected caerulein induced suppression of amylase output. This effect was reproduced by indazole and capsaicin. Indazole did not alter responses to either optimal (0.25 micro g/kg) or suboptimal (0.1 micro g/kg) caerulein, nor, in contrast with L-NAME, aggravate the outcome of caerulein induced pancreatitis.

Conclusions

Reduction of circulating NO availability, probably of endothelial origin, is responsible for the decrease in amylase secretion observed in the early response to L-NAME. Nitrergic neuro-transmission plays an important role in the control of pancreatic secretion and may induce opposite effects to endothelial NOS activity.

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