胆碱能神经源性血管舒张由一氧化氮介导于犬后肢。

Cholinergic neurogenic vasodilatation is mediated by nitric oxide in the dog hindlimb.

作者信息

Loke K E, Sobey C G, Dusting G J, Woodman O L

机构信息

Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.

出版信息

Cardiovasc Res. 1994 Apr;28(4):542-7. doi: 10.1093/cvr/28.4.542.

DOI:10.1093/cvr/28.4.542

PMID:8181044

Abstract

OBJECTIVE

The aim was to investigate the role of nitric oxide (NO) in cholinergic neurogenic vasodilatation in the dog hindlimb using the NO synthase inhibitor, N-nitro-L-arginine (NOLA), and the NO precursor, L-arginine.

METHODS

20 dogs were anaesthetised with thiopentone and alpha chloralose and experiments were performed in the presence of noradrenergic neurone blockade with guanethidine (15 mg.kg-1 subcutaneously). Using stereotaxic procedures, specific sites in the hypothalamus were electrically stimulated (HS) to produce depressor and hindlimb vasodilator responses. In each experiment, responses to intra-arterial (ia) injections of acetylcholine and glyceryl trinitrate produced increases in femoral blood flow similar to those caused by HS.

RESULTS

Vasodilator responses to HS and acetylcholine but not glyceryl trinitrate were reduced by the muscarinic receptor antagonists tropicamide (3-12 mg ia) or atropine (0.5 mg.kg-1 intravenously, i.v.). Administration of NOLA (5-15 mg.kg-1 ia) significantly attenuated the HS induced decrease in arterial pressure [delta AP: control = -21 (SEM 3) mm Hg v NOLA treated = -9(3) mm Hg, p < 0.005] and the increase in femoral blood flow [delta FBF: control = 43(7) ml.min-1 v NOLA treated = 17(4) ml.min-1, p < 0.005]. NOLA also significantly inhibited femoral vasodilator responses to acetylcholine [delta FBF: control = 47(6) ml.min-1 v NOLA treated = 35(6) ml.min-1, p < 0.05] whereas responses to glyceryl trinitrate were enhanced [delta FBF: control = 54(9) ml.min-1 v NOLA treated = 69(9) ml.min-1, p < 0.005]. In addition L-arginine (150-300 mg.kg-1 i.v.), but not D-arginine (150 mg.kg-1 i.v.), reversed the inhibitory effect of NOLA on HS induced dilator responses [delta FBF: NOLA treated = 14(4) ml.min-1 v L-arginine treated = 35(8) ml.min-1, n = 8; greater than NOLA treated, p < 0.05].

CONCLUSIONS

Vasodilatation in the dog hindlimb evoked by activation of cholinergic nerves involves the synthesis of NO; however the source of this NO remains to be determined.

摘要

目的

旨在使用一氧化氮合酶抑制剂N-硝基-L-精氨酸（NOLA）和一氧化氮前体L-精氨酸，研究一氧化氮（NO）在犬后肢胆碱能神经源性血管舒张中的作用。

方法

20只犬用硫喷妥钠和α-氯醛糖麻醉，并在使用胍乙啶（15mg·kg-1皮下注射）阻断去甲肾上腺素能神经元的情况下进行实验。采用立体定位程序，电刺激下丘脑的特定部位（HS）以产生降压和后肢血管舒张反应。在每个实验中，动脉内（ia）注射乙酰胆碱和硝酸甘油所产生的反应使股血流量增加，类似于HS所引起的增加。

结果

毒蕈碱受体拮抗剂托吡卡胺（3 - 12mg ia）或阿托品（0.5mg·kg-1静脉注射，i.v.）可降低对HS和乙酰胆碱的血管舒张反应，但对硝酸甘油的反应无影响。给予NOLA（5 - 15mg·kg-1 ia）可显著减弱HS诱导的动脉压下降[ΔAP：对照组 = -21（SEM 3）mmHg，NOLA处理组 = -9（3）mmHg，p < 0.005]以及股血流量增加[ΔFBF：对照组 = 43（7）ml·min-1，NOLA处理组 = 17（4）ml·min-1，p < 0.005]。NOLA还显著抑制股动脉对乙酰胆碱的血管舒张反应[ΔFBF：对照组 = 47（6）ml·min-1，NOLA处理组 = 35（6）ml·min-1，p < 0.05]，而对硝酸甘油反应增强[ΔFBF：对照组 = 54（9）ml·min-1，NOLA处理组 = 69（9）ml·min-1，p < 0.005]。此外，L-精氨酸（150 - 300mg·kg-1静脉注射）而非D-精氨酸（150mg·kg-1静脉注射）可逆转NOLA对HS诱导的舒张反应的抑制作用[ΔFBF：NOLA处理组 = 14（4）ml·min-1，L-精氨酸处理组 = 35（8）ml·min-1，n = 8；大于NOLA处理组，p < 0.05]。