Tanaka Y, Otsuka A, Tanaka H, Shigenobu K
Department of Pharmacology, Toho University School of Pharmaceutical Sciences, Funabashi-City, Chiba, Japan.
Res Commun Mol Pathol Pharmacol. 1999 Mar;103(3):227-39.
Pharmacological characteristics of non-prostanoid (PGI2), non-NO mediated endothelium-dependent relaxation in response to acetylcholine (ACh) were examined in the isolated rat mesenteric artery, especially focusing on the possible contribution of the gap junctional communication in the response. ACh produced an endothelium-dependent relaxation of the isolated rat mesenteric artery with functional endothelium in the presence of both indomethacin (3 x 10(-6) M) and N(G)-nitro-L-arginine methyl ester (L-NAME) (10(-4) M), an inhibitor of nitric oxide synthase (NOS). ACh-induced relaxation of the rat mesenteric artery in the presence of indomethacin and L-NAME was strongly attenuated in the solution containing high (80 mM) KCl, tetraethylammonium (TEA) (10(-2) M), which suggests the involvement of endothelium-derived relaxing factor(s) (EDHF(s)) in the response. Non-PGI2, non-NO mediated endothelium-dependent relaxation to ACh was not profoundly affected by glibenclamide (10(-6) M), 4-aminopyridine (4-AP) (10(-4) M), iberiotoxin (10(-7) M), agitoxin-2 (10(-8) M), or apamin (10(-7) M), but was abolished by the treatment with apamin (10(-7) M) plus charybdotoxin (10(-7) M). Non-PGI2, non-NO mediated endothelium-dependent relaxation to ACh was not substantially affected by arachidonic acid (AA) (10(-4) M) or ONO-RS-082 (10(-5) M), an inhibitor of phospholipase A2, which rules out the involvement of AA metabolites in the vascular response. Furthermore, a gap junction inhibitor, 18alpha-glycyrrhetinic acid (18alpha-GA) did not show dramatic inhibitory effect on non-PGI2, non-NO mediated endothelium-dependent relaxation induced by ACh. These findings suggest that 1) metabolites of AA are not involved in non-PGI2, non-NO mediated endothelium-dependent relaxation to ACh in the isolated rat mesenteric artery; 2) Heterocellular gap junctional communication does not mainly account for non-PGI2, non-NO mediated endothelium-dependent relaxation evoked by ACh in this artery.
在离体大鼠肠系膜动脉中研究了非前列腺素（PGI2）、非一氧化氮（NO）介导的对乙酰胆碱（ACh）的内皮依赖性舒张的药理学特性，尤其关注缝隙连接通讯在该反应中的可能作用。在吲哚美辛（3×10⁻⁶ M）和一氧化氮合酶（NOS）抑制剂N(G)-硝基-L-精氨酸甲酯（L-NAME）（10⁻⁴ M）存在的情况下，ACh使具有功能性内皮的离体大鼠肠系膜动脉产生内皮依赖性舒张。在含有高浓度（80 mM）氯化钾、四乙铵（TEA）（10⁻² M）的溶液中，吲哚美辛和L-NAME存在时ACh诱导的大鼠肠系膜动脉舒张作用明显减弱，这表明内皮源性舒张因子（EDHF）参与了该反应。非PGI2、非NO介导的对ACh的内皮依赖性舒张不受格列本脲（10⁻⁶ M）、4-氨基吡啶（4-AP）（10⁻⁴ M）、iberiotoxin（10⁻⁷ M）、agitoxin-2（10⁻⁸ M）或蜂毒明肽（10⁻⁷ M）的显著影响，但用蜂毒明肽（10⁻⁷ M）加蝎毒素（10⁻⁷ M）处理可消除该舒张作用。非PGI2、非NO介导的对ACh的内皮依赖性舒张不受花生四烯酸（AA）（10⁻⁴ M）或磷脂酶A2抑制剂ONO-RS-082（10⁻⁵ M）的实质性影响，这排除了AA代谢产物参与血管反应的可能性。此外，缝隙连接抑制剂18α-甘草次酸（18α-GA）对ACh诱导的非PGI2、非NO介导的内皮依赖性舒张未显示出显著抑制作用。这些发现表明：1）AA代谢产物不参与离体大鼠肠系膜动脉中非PGI2、非NO介导的对ACh的内皮依赖性舒张；2）异细胞缝隙连接通讯并非该动脉中ACh诱发的非PGI2、非NO介导的内皮依赖性舒张的主要原因。
Zotero 插件