Toda N, Toda M, Ayajiki K, Okamura T
Department of Pharmacology, Shiga University of Medical Science, Ohtsu, Japan.
Am J Physiol. 1998 May;274(5):H1582-9. doi: 10.1152/ajpheart.1998.274.5.H1582.
We sought to determine the control of ciliary arterial tone by neurogenic acetylcholine (ACh) acting directly on smooth muscle and in conjunction with vasodilator nerves. Isolated posterior ciliary arteries from monkeys responded to ACh (10(-8)-10(-5) M) with dose-related contractions, which were endothelium independent. The response was not affected by cyclooxygenase inhibitors but was abolished by atropine. Relaxations induced at 10(-4) M ACh in the atropine-treated arterial strips were abolished by hexamethonium and NG-nitro-L-arginine (L-NNA), and L-arginine (L-Arg) reversed the response suppressed by L-NNA. Similar results were also obtained on the nicotine (10(-4) M)-induced relaxation. Contractions due to transmural electrical stimulation in the endothelium-denuded strips treated with L-NNA were potentiated by physostigmine and depressed by atropine; the remaining contraction in the presence of atropine was abolished by prazosin. Relaxations associated with electrical stimulation, sensitive to tetrodotoxin, were abolished or reversed to contractions by L-NNA and restored by L-Arg. Stimulation-induced relaxation was attenuated by exogenous ACh and physostigmine and was potentiated by atropine. ACh did not affect the relaxation caused by nitric oxide (NO). Nerve fibers and bundles containing NADPH diaphorase and acetylcholinesterase were histologically demonstrated in the adventitia of ciliary arteries. We conclude that 1) endogenous and exogenous ACh contracts monkey ciliary arteries by acting on muscarinic receptors in smooth muscle cell membranes, 2) vasodilatation elicited by nerve stimulation with electrical pulses or nicotine is mediated by NO synthesized from L-Arg, 3) neurogenic ACh seems to interfere with the nitroxidergic nerve function by acting on prejunctional muscarinic receptors, and 4) high concentrations of ACh stimulate nicotinic receptors in vasodilator nerve terminals and promote the synthesis and/or release of NO.
我们试图确定神经源性乙酰胆碱（ACh）直接作用于平滑肌以及与血管舒张神经协同作用时对睫状动脉张力的控制。从猴子身上分离出的后睫状动脉对ACh（10⁻⁸ - 10⁻⁵ M）产生剂量相关的收缩反应，该反应不依赖于内皮。该反应不受环氧化酶抑制剂的影响，但被阿托品消除。在经阿托品处理的动脉条中，10⁻⁴ M ACh诱导的舒张反应被六甲铵和NG-硝基-L-精氨酸（L-NNA）消除，而L-精氨酸（L-Arg）可逆转被L-NNA抑制的反应。在尼古丁（10⁻⁴ M）诱导的舒张反应中也获得了类似结果。在用L-NNA处理的内皮剥脱条中，经皮电刺激引起的收缩被毒扁豆碱增强，被阿托品抑制；在阿托品存在下剩余的收缩被哌唑嗪消除。与电刺激相关的、对河豚毒素敏感的舒张反应被L-NNA消除或逆转成收缩反应，并被L-Arg恢复。刺激诱导的舒张反应被外源性ACh和毒扁豆碱减弱，并被阿托品增强。ACh不影响一氧化氮（NO）引起的舒张。在睫状动脉外膜中组织学证实存在含有NADPH黄递酶和乙酰胆碱酯酶的神经纤维和神经束。我们得出结论：1）内源性和外源性ACh通过作用于平滑肌细胞膜上的毒蕈碱受体使猴子睫状动脉收缩；2）电脉冲或尼古丁神经刺激引起的血管舒张由L-Arg合成的NO介导；3）神经源性ACh似乎通过作用于节前毒蕈碱受体干扰硝氧化物能神经功能；4）高浓度ACh刺激血管舒张神经末梢的烟碱受体并促进NO的合成和/或释放。
