SKF-525A不抑制大鼠胸主动脉、狗肠系膜和股动脉内皮源性松弛因子的释放。

Blood vessels Pub Date : 1991-01-01 DOI:10.1159/000158894
J M Xie, Y Wang, S S Greenberg
{"title":"SKF-525A不抑制大鼠胸主动脉、狗肠系膜和股动脉内皮源性松弛因子的释放。","authors":"J M Xie,&nbsp;Y Wang,&nbsp;S S Greenberg","doi":"10.1159/000158894","DOIUrl":null,"url":null,"abstract":"<p><p>SKF-525A (proadifen) inhibits endothelium-dependent relaxations induced by acetylcholine, arachidonic acid and the calcium ionophore A23187. This suggests that SKF-525A is an inhibitor of endothelium-derived relaxing factor (EDRF) and that EDRF may be a product of arachidonic acid metabolism formed via a cytochrome P-450-dependent pathway or that EDRF release is dependent on cytochrome P-450. We tested this postulate using both isolated rings of rat thoracic aorta and dog mesenteric and femoral artery and the perfusion-superfusion bioassay. Rings of rat thoracic aorta and dog mesenteric and femoral artery with intact endothelium were precontracted with an EC50 concentration of norepinephrine (0.1 nmol/l) or U46619 (0.05 mumol/l) and the relaxation to acetylcholine (ACh), bradykinin, adenosine triphosphate (ATP) or nitroglycerin (GTN) were obtained before, 30 min after addition of, and 30 min after washout of SKF-525A (50 mumol/l). SKF-525A inhibited ACh-induced endothelium-dependent relaxation of rat aortic rings and endothelium-dependent relaxation of the dog mesenteric and femoral artery produced by ACh and ATP, but did not affect relaxation to bradykinin or GTN. The inhibitory effect on SKF-525A on ACh and ATP-induced relaxation was partially reversed upon its washout from the muscle chamber. Pretreatment of the blood vessels with ibuprofen (1 mumol/l) did not attenuate SKF-525A-mediated inhibition of the relaxations to any agonist. Selective exposure of dog femoral artery (donor) to SKF-525A (50 mumol/l) for 60 min did not affect the relaxation responses of endothelium-rubbed coronary artery (bioassay tissue) to basal EDRF nor to the effluent from donor tissues stimulated with ACh (10-1,000 pmol), ATP (1-100 nmol) or bradykinin (3-100 pmol). The results show that SKF-525A exhibited a reversible inhibition of endothelium-dependent relaxation by a smooth muscle mechanism unrelated to the generation of EDRF from endothelium.</p>","PeriodicalId":9009,"journal":{"name":"Blood vessels","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"1991-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000158894","citationCount":"1","resultStr":"{\"title\":\"SKF-525A does not inhibit release of endothelium-derived relaxing factor from rat thoracic aorta and dog mesenteric and femoral artery.\",\"authors\":\"J M Xie,&nbsp;Y Wang,&nbsp;S S Greenberg\",\"doi\":\"10.1159/000158894\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>SKF-525A (proadifen) inhibits endothelium-dependent relaxations induced by acetylcholine, arachidonic acid and the calcium ionophore A23187. This suggests that SKF-525A is an inhibitor of endothelium-derived relaxing factor (EDRF) and that EDRF may be a product of arachidonic acid metabolism formed via a cytochrome P-450-dependent pathway or that EDRF release is dependent on cytochrome P-450. We tested this postulate using both isolated rings of rat thoracic aorta and dog mesenteric and femoral artery and the perfusion-superfusion bioassay. Rings of rat thoracic aorta and dog mesenteric and femoral artery with intact endothelium were precontracted with an EC50 concentration of norepinephrine (0.1 nmol/l) or U46619 (0.05 mumol/l) and the relaxation to acetylcholine (ACh), bradykinin, adenosine triphosphate (ATP) or nitroglycerin (GTN) were obtained before, 30 min after addition of, and 30 min after washout of SKF-525A (50 mumol/l). SKF-525A inhibited ACh-induced endothelium-dependent relaxation of rat aortic rings and endothelium-dependent relaxation of the dog mesenteric and femoral artery produced by ACh and ATP, but did not affect relaxation to bradykinin or GTN. The inhibitory effect on SKF-525A on ACh and ATP-induced relaxation was partially reversed upon its washout from the muscle chamber. Pretreatment of the blood vessels with ibuprofen (1 mumol/l) did not attenuate SKF-525A-mediated inhibition of the relaxations to any agonist. Selective exposure of dog femoral artery (donor) to SKF-525A (50 mumol/l) for 60 min did not affect the relaxation responses of endothelium-rubbed coronary artery (bioassay tissue) to basal EDRF nor to the effluent from donor tissues stimulated with ACh (10-1,000 pmol), ATP (1-100 nmol) or bradykinin (3-100 pmol). The results show that SKF-525A exhibited a reversible inhibition of endothelium-dependent relaxation by a smooth muscle mechanism unrelated to the generation of EDRF from endothelium.</p>\",\"PeriodicalId\":9009,\"journal\":{\"name\":\"Blood vessels\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1991-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1159/000158894\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Blood vessels\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1159/000158894\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Blood vessels","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1159/000158894","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 1

摘要

SKF-525A (proadifen)抑制乙酰胆碱、花生四烯酸和钙离子载体A23187诱导的内皮依赖性松弛。这表明SKF-525A是内皮衍生放松因子(EDRF)的抑制剂,EDRF可能是花生四烯酸代谢的产物,通过细胞色素P-450依赖途径形成,或者EDRF的释放依赖于细胞色素P-450。我们用大鼠胸主动脉和狗肠系膜和股动脉分离环以及灌注-灌注生物测定法来验证这一假设。分别用EC50浓度的去甲肾上腺素(0.1 nmol/l)或U46619 (0.05 mumol/l)对内皮完整的大鼠胸主动脉和狗肠系膜、股动脉环进行预收缩,分别在SKF-525A (50 mumol/l)加入前、加入后30 min和冲洗后30 min获得对乙酰胆碱(ACh)、弛豫素、三磷酸腺苷(ATP)或硝酸甘油(GTN)的松弛。SKF-525A抑制乙酰胆碱诱导的大鼠主动脉环内皮依赖性松弛和乙酰胆碱和ATP诱导的狗肠系膜和股动脉内皮依赖性松弛,但不影响对缓激肽或GTN的松弛。SKF-525A对乙酰胆碱和atp诱导的松弛的抑制作用在其从肌室洗脱后部分逆转。用布洛芬(1mumol /l)预处理血管不会减弱skf - 525a介导的对任何激动剂的松弛抑制。犬股动脉(供体)选择性暴露于SKF-525A (50 μ mol/l)中60分钟,不影响内皮摩擦冠状动脉(生物测定组织)对基础EDRF的松弛反应,也不影响供体组织对乙酰胆碱(10-1,000 pmol)、ATP (1-100 nmol)或缓激肽(3-100 pmol)刺激的流出物的松弛反应。结果表明,SKF-525A通过与内皮生成EDRF无关的平滑肌机制对内皮依赖性松弛表现出可逆的抑制作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
SKF-525A does not inhibit release of endothelium-derived relaxing factor from rat thoracic aorta and dog mesenteric and femoral artery.

SKF-525A (proadifen) inhibits endothelium-dependent relaxations induced by acetylcholine, arachidonic acid and the calcium ionophore A23187. This suggests that SKF-525A is an inhibitor of endothelium-derived relaxing factor (EDRF) and that EDRF may be a product of arachidonic acid metabolism formed via a cytochrome P-450-dependent pathway or that EDRF release is dependent on cytochrome P-450. We tested this postulate using both isolated rings of rat thoracic aorta and dog mesenteric and femoral artery and the perfusion-superfusion bioassay. Rings of rat thoracic aorta and dog mesenteric and femoral artery with intact endothelium were precontracted with an EC50 concentration of norepinephrine (0.1 nmol/l) or U46619 (0.05 mumol/l) and the relaxation to acetylcholine (ACh), bradykinin, adenosine triphosphate (ATP) or nitroglycerin (GTN) were obtained before, 30 min after addition of, and 30 min after washout of SKF-525A (50 mumol/l). SKF-525A inhibited ACh-induced endothelium-dependent relaxation of rat aortic rings and endothelium-dependent relaxation of the dog mesenteric and femoral artery produced by ACh and ATP, but did not affect relaxation to bradykinin or GTN. The inhibitory effect on SKF-525A on ACh and ATP-induced relaxation was partially reversed upon its washout from the muscle chamber. Pretreatment of the blood vessels with ibuprofen (1 mumol/l) did not attenuate SKF-525A-mediated inhibition of the relaxations to any agonist. Selective exposure of dog femoral artery (donor) to SKF-525A (50 mumol/l) for 60 min did not affect the relaxation responses of endothelium-rubbed coronary artery (bioassay tissue) to basal EDRF nor to the effluent from donor tissues stimulated with ACh (10-1,000 pmol), ATP (1-100 nmol) or bradykinin (3-100 pmol). The results show that SKF-525A exhibited a reversible inhibition of endothelium-dependent relaxation by a smooth muscle mechanism unrelated to the generation of EDRF from endothelium.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
期刊最新文献
Contractile and morphologic properties of a saphenous vein after 12 years as an aortocoronary bypass graft. Effect of H-8, an isoquinolinesulfonamide inhibitor of cyclic nucleotide-dependent protein kinase, on cAMP- and cGMP-mediated vasorelaxation. Hemorheological effects of buflomedil: action on shape and functions of the human neutrophils. Norepinephrine, phentolamine and buflomedil influence on arteriolar vasomotion in the hamster skinfold preparation. Heme-dependent activation of guanylate cyclase by nitric oxide: a novel signal transduction mechanism.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1