Wang Y, Okamura T, Toda N
Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
Exp Eye Res. 1993 Sep;57(3):275-81. doi: 10.1006/exer.1993.1125.
Mechanisms underlying the relaxant response to acetylcholine (ACh) were examined in dog external (EOA) and internal ophthalmic arteries (IOA). Acetylcholine produced relaxation in EOA and IOA, partially contracted with prostaglandin (PG) F2 alpha. The relaxations induced by ACh in these arteries were not inhibited by endothelium denudation. The ACh (10(-8)-10(-5) M)-induced relaxations in EOA and IOA were abolished by treatment with atropine or indomethacin and markedly suppressed by tranylcypromine, a PGI2 synthesis inhibitor, but not influenced by hexamethonium. On the other hand, the relaxant response to the highest concentration used (10(-4) M) was partially attenuated but not abolished by treatment with atropine, indomethacin or hexamethonium. This relaxation under treatment with atropine was abolished by NG-nitro-L-arginine (L-NA), a nitric oxide synthase inhibitor, but not by indomethacin, whereas the response under treatment with hexamethonium was abolished by indomethacin, but not by L-NA. Combined treatment with indomethacin and L-NA or oxyhaemoglobin abolished the ACh (10(-4) M)-induced relaxation, or reversed it to a contraction. It may be concluded that relaxations induced by low concentrations of ACh in dog EOA and IOA are associated possibly with the release of PGI2 through activation of muscarinic receptors located in subendothelial tissues, including smooth muscle, and the relaxant response to the high concentration (10(-4) M) of ACh is mediated mainly by the release of nitric oxide through activation of nicotinic receptors in nitroxidergic nerves.
研究了犬眼外动脉（EOA）和眼内动脉（IOA）对乙酰胆碱（ACh）产生舒张反应的机制。乙酰胆碱可使EOA和IOA舒张，这两条动脉已用前列腺素（PG）F2α使其部分收缩。ACh在这些动脉中诱导的舒张不受内皮剥脱的抑制。ACh（10⁻⁸ - 10⁻⁵ M）在EOA和IOA中诱导的舒张可被阿托品或吲哚美辛处理所消除，并被PGI2合成抑制剂反苯环丙胺显著抑制，但不受六甲铵影响。另一方面，对所用最高浓度（10⁻⁴ M）的舒张反应经阿托品、吲哚美辛或六甲铵处理后部分减弱但未被消除。阿托品处理后的这种舒张被一氧化氮合酶抑制剂NG-硝基-L-精氨酸（L-NA）消除，但不受吲哚美辛影响，而六甲铵处理后的反应被吲哚美辛消除，但不受L-NA影响。吲哚美辛与L-NA或氧合血红蛋白联合处理可消除ACh（10⁻⁴ M）诱导的舒张，或将其逆转至收缩。可以得出结论，低浓度ACh在犬EOA和IOA中诱导的舒张可能与通过激活位于包括平滑肌在内的内皮下组织中的毒蕈碱受体释放PGI2有关，而对高浓度（10⁻⁴ M）ACh的舒张反应主要由通过激活硝氧能神经中的烟碱受体释放一氧化氮介导。
