Role of nitric oxide in the pancreatic vascular and metabolic responses associated with activation of capsaicin-sensitive neurons.

The effects of local periarterial placement of capsaicin upon pancreatic blood flow, oxygen extraction from pancreatic circulation and oxygen consumption by pancreatic tissue were measured in anesthetized dogs. These studies explored also the possible role of endogenous nitric oxide (NO) in the pancreatic vascular and metabolic responses to periarterial capsaicin. In anesthetized dogs, superior pancreatico-doudenal artery blood flow (SPBF) was measured with an ultrasonic blood flowmeter. Microcirculatory pancreatic blood flow (PBF) was measured with laser-Doppler flowmeter. Arteriovenous oxygen difference (AVO2) across the pancreatic circulation was determined spectrophotometrically. Pancreatic oxygen uptake was calculated as the product of AVO2 and SPBF. Capsaicin applied periarterialy induced initial increase in SPBF, PBF and oxygen uptake. The acute capsaicin-induced vascular dilation was followed by steady state response characterized by significant decrease in SPBF, PBF and oxygen uptake. Inhibition of NO synthase by N omega-nitro-L-arginine (L-NNA) induced pancreatic ischemia and hypoxia. After pretreatment with L-NNA the acute capsaicin-induced pancreatic vascular dilation and the increase in pancreatic oxygen uptake were significantly reduced. Above circulatory and metabolic effects of L-NNA were significantly attenuated when administration of L-NNA was combined with L-arginine. The results of these studies indicate that sensory C-fibers at rest and when activated play a role in the control of pancreatic blood flow and tissue oxygenation. These findings support also the hypothesis that NO plays a role in the mediation of pancreatic vasodilatory action of neuropeptides released from sensory C-fibers.