远端食管黏膜血流的调节：一氧化氮和P物质的作用。

Regulation of distal esophageal mucosal blood flow: the roles of nitric oxide and substance P.

作者信息

Sandler A D, Schmidt C, Richardson K, Murray J, Maher J W

机构信息

Department of Surgery, University of Iowa College of Medicine, Iowa City.

出版信息

Surgery. 1993 Aug;114(2):285-93; discussion 293-4.

PMID:7688153

Abstract

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 changes in MBF and the regulation thereof after intraluminal application of noxious chemical stimuli. The role, if any, of substance P (SP) and nitric oxide (NO), two potent vasodilatory substances, and the vascular 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 before and after topical application of HCl (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 denervation procedures were used to delineate the mechanisms that regulate MBF.

RESULTS

Sequential luminal applications of hydrochloric acid (HCl) or a single application of capsaicin increased MBF (p < 0.01). Topical intraluminal lidocaine blocked the response to capsaicin (p > 0.2) but not to HCl (p < 0.05). Abrupt increases in MBF occurred with intraarterial SP or bradykinin (p < 0.01). Neither atropine nor truncal vagotomy blocked the increase in MBF from these peptides or noxious stimuli. The NO synthesis antagonist NG-nitro-L-arginine methyl ester (L-NAME) blocked the response to bradykinin and attenuated the response to HCl (p < 0.05). NG-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 applications of HCl or capsaicin appear to stimulate increases in esophageal MBF by different mechanisms. HCl produces an adaptive response that appears dependent on the paracrine effect of NO. Capsaicin-sensitive neurons mediate vasodilation through SP neurotransmission, independent of extrinsic vagal or cholinergic innervation.

摘要

背景

食管黏膜血流量（MBF）增加可能是一种重要的保护机制，可抵御摄入或反流的有害因子对黏膜的损伤。本研究调查了腔内应用有害化学刺激后MBF的变化及其调节机制。评估了两种强效血管舒张物质P物质（SP）和一氧化氮（NO）的作用，以及SP在食管远端的血管分布。

方法

在麻醉犬身上，使用连接测压和pH探头的激光多普勒血流探头测量食管MBF。在食管远端局部应用盐酸（2ml；1N）或辣椒素（2ml；0.5%）前后测量MBF。还测定了动脉内注射SP和缓激肽对MBF的影响。使用药理学拮抗剂和去神经手术来阐明调节MBF的机制。

结果

依次腔内应用盐酸（HCl）或单次应用辣椒素可增加MBF（p<0.01）。腔内局部应用利多卡因可阻断对辣椒素的反应（p>0.2），但不能阻断对HCl的反应（p<0.05）。动脉内注射SP或缓激肽后MBF会突然增加（p<0.01）。阿托品或迷走神经干切断术均不能阻断这些肽或有害刺激引起的MBF增加。NO合成拮抗剂NG-硝基-L-精氨酸甲酯（L-NAME）可阻断对缓激肽的反应，并减弱对HCl的反应（p<0.05）。NG-硝基-L-精氨酸甲酯不影响对SP或辣椒素的反应。一种P物质拮抗剂可阻断辣椒素（p>0.6）和SP（p>0.1）的作用，但不能阻断HCl（p<0.01）或缓激肽（p>0.01）的作用。