ROLE OF NITRIC-OXIDE IN THE PANCREATIC BLOOD-FLOW RESPONSE TO CERULEIN

To clarify the role of nitric oxide (NO) in the pancreas, blood flow in the rat pancreas (pancreatic blood flow: PBF) was investigated by the hydrogen clearance technique using a specific NO synthase inhibitor, N-omega-nitro-L-arginine (L-NNA). Continuous infusion of caerulein at doses of 5 and 20 mu g/kg/h caused a significant increase in PBF in the early phase of caerulein infusion. The caerulein-induced increase in PBF was not affected significantly by atropine sulfate (100 mu g/kg), nor by phenoxybenzamine (5 mg/kg) plus propranolol (50 mu g/kg). Administration of L-NNA (0.5, 5, or 30 mg/kg) did not affect the basal PBF, but at 5 mg/kg it inhibited completely the caerulein-induced increase in PBF. The inhibitory action of L-NNA was reversed by a large dose of L-arginine (100 mg/kg bolus, i.v., followed by a continuous infusion at 400 mg/kg/h), but not by its enantiomer D-arginine. These results strongly suggest that NO has a mediator role in the early phase vascular response of the pancreas to superphysiologic doses of caerulein.