REGULATION OF DISTAL ESOPHAGEAL MUCOSAL BLOOD-FLOW - THE ROLES OF NITRIC-OXIDE AND SUBSTANCE-P

Background. An increase in esophageal mucosal blood flow (MBF) may be an important protective mechanism against mucosal injury from noxious agents that are ingested or refluxed. This study investigated the chan ges in MBF and the regulation thereof after intraluminal application o f noxious chemical stimuli. The role, if any, of substance P (SP) and nitric oxide (NO), two potent vasodilatory substances, and the vascula r distribution of SP in the distal esophagus were evaluated. Methods. Esophageal MBF was measured in anesthetized dogs with a laser Doppler flow probe attached to manometry and pH probes. MBF was measured befor e and after topical application of HCI (2 ml; 1N) or capsaicin (2 ml; 0.5%) in the distal esophagus. The effects on MBF of intraarterial SP and bradykinin were also determined. Pharmacologic antagonists and den ervation procedures were used to delineate the mechanisms that regulat e MBF. Results. Sequential luminal applications of hydrochloric acid ( HCl) or a single application of capsaicin increased MBF (p < 0.01). To pical intraluminal lidocaine blocked the response to capsaicin (p > 0. 2) but not to HCl (p < 0.05). Abrupt increases in MBF occurred with in traarterial SP or bradykinin (p < 0.01). Neither atropine nor truncal vagotomy blocked the increase in MBF from these peptides or noxious st imuli. The NO synthesis antagonist N(G)-nitro-L-arginine methyl ester (L-NAME) blocked the response to bradykinin and attenuated the respons e to HCl (p < 0.05). N(G)-nitro-L-arginine methyl ester did not affect the response to SP or capsaicin. A substance P antagonist blocked the effects of both capsaicin (p > 0.6) and SP (p > 0.1) but not that of HCl (p < 0.01) or bradykinin (p > 0.01). Conclusions. Intraluminal app lications of HCI or capsaicin appear to stimulate increases in esophag eal MBF by different mechanisms. HCI produces an adaptive response tha t appears dependent on the paracrine effect of NO. Capsaicin-sensitive neurons mediate vasodilation through SP neurotransmission, independen t of extrinsic vagal or cholinergic innervation.