Role of nitric oxide in the pancreatic blood flow response to caerulein

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 micrograms/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 micrograms/kg), nor by phenoxybenzamine (5 mg/kg) plus propranolol (50 micrograms/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.