Effect of central thyrotropin-releasing hormone on pancreatic blood flow in rats

Central neuropeptides play a role in physiological regulation through the autonomic nervous system. Thyrotropin-releasing hormone (TRH) is a neuropeptide distributed throughout the central nervous system and acts as a neurotransmitter to regulate gastric and hepatic functions through vagal-cholinergic pathways. In this study, the central effect of TRH on pancreatic blood flow was investigated in urethane-anesthetized rats. Pancreatic blood flow was determined by laser Doppler flowmetery. After measurement of basal blood flow, a stable TRH analog, RX 77368 (1-50 ng) or saline was injected intracisternally. Pancreatic blood flow was observed for 120 min thereafter. In some experiments, pretreatment with atropine methyl nitrate (0.15 mg/kg, i.p.), NG-nitro-L-arginine-methyl ester (10 mg/kg, i.v.), or 6-hydroxydopamine (6-OHDA;180 mg/kg, i.p.), or subdiaphragmatic vagotomy was performed. Intracisternal injection of TRH analog dose-dependently increased pancreatic blood flow with a peak response occurring 30 min after injection. The stimulatory effect of TRH analog on pancreatic blood flow was blocked by vagotomy, atropine, and NG-nitro-L-arginine-methyl ester, but not by 6-hydroxydopamine. Intravenous administration of the TRH analog did not influence pancreatic blood flow in the same animal model. These results indicate that TRH acts in the central nervous system to stimulate pancreatic blood flow through vagal-cholinergic and nitric oxide-dependent pathways.