A PHARMACOLOGICAL STUDY ON THE INTERACTIONS BETWEEN VASOACTIVE AUTACOIDS INVOLVING ENDOTHELIAN CELLS

血管活性类固醇与内皮细胞相互作用的药理学研究

• 批准号: 04670571
• 负责人: MATSUDA Hisao
• 金额: $ 1.34万
• 依托单位: NATIIONAL CARDIOVASCULAR CENTER RESEARCH INSTITUTE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670571/
• 关键词: Endothelium; Perivascular Nerve Stimulation; Endothelin; Nitric Oxide; Eicosanoid; Perivascular Nerve Stimulatioan; Endothelina; Periarterial Nerve Stimulation

The present study attempted to examine the regulatory mechanism of vascular smooth muscular tone based on neuroeffector-endothelial interaction, employing isolated vascular tissue with the use of perivascular nerve stimulation (PNS). As a result, it is indicated that nitric oxide (NO)might be released on PNS and modulate autonomic adrenergic neurotransmision in guinea pig arteries (pulmonary and iliac artery). In guinea pig pulmonary artery, sensory neuropeptides (calcitonin gene-related peptide and substance P) are also indicated to be released on PNS and participate in modulation of autonomic adrenergic neurotransmission.The mechanism of PNS-induced release of NO was further investigated and it was indicated that noradrenaline released on PNS could act onendothelium resulting in release of NO.Sensory neuropeptides released on PNS could also participate in endothelial NO release. Additionally, a dilator nerve relasing NO was indicated in guinea pig pulmonary artery. With respect to the mode of endothelin (ET)-1 action, the invivo investigation was done. As a result, secondary release of cyclo-oxygenase-generated eicosanoid(s), mainly thromboxane A_2 was suggested to be responsible for the pressor response of ET-1. The interactions between ET-1 and other vasoactive autacoids were examined employing cultured endothelial cells and increase in the level of prostacyclin (6-keto-prostaglandin F_<1alpha>) was observed in the culture media after administration of endothelin-1. The interactions between other autacoids are being investigated.

本研究试图研究血管平滑肌张力的调节机制的基础上的神经效应器-内皮细胞的相互作用，采用离体血管组织与使用血管周围神经刺激（PNS）。结果表明，三七总皂甙可释放一氧化氮（NO），调节豚鼠肺动脉和髂动脉的自主肾上腺素能神经传递。在豚鼠肺动脉，感觉神经肽PNS还可释放降钙素基因相关肽（calcitonin gene-related peptide，CGRP）和P物质（substance P），参与自主肾上腺素能神经传递的调节。进一步研究了PNS对NO的诱导释放，结果表明PNS释放的去甲肾上腺素可作用于内皮细胞，导致NO的释放，PNS释放的感觉神经肽也可参与内皮细胞NO的释放release.此外，在豚鼠肺动脉中还发现了释放NO的扩张神经。对内皮素（ET）-1的作用方式进行了体内研究。结果表明，ET-1的升压反应可能是由环氧合酶产生的类二十烷酸，主要是血栓素A_2的次级释放引起的。采用培养的内皮细胞检测ET-1与其他血管活性自育素之间的相互作用，并观察到给予内皮素-1后培养液中前列环素（6-酮-前列腺素F_）水平的增加<1alpha>。其他autacoids之间的相互作用正在研究中。

项目成果

Hisao Matsuda et al.: "An experimental study on non-adrenergic and non-cholinergic modulation of adrenergic neurotransmission in vascular tissue" Progress in Microcirculation Research Elsevier Science. 4 (1994)

Hisao Matsuda 等人：“血管组织中肾上腺素能神经传递的非肾上腺素能和非胆碱能调节的实验研究”微循环研究进展爱思唯尔科学。

Hisao Matsuda et al.: "A comparative study on the sites of nitric oxide release on perivascular nerve stimulation in different arteries from guinea pig" Endothelium. Vol. 2 (inpress). (1994)

Hisao Matsuda 等人：“豚鼠不同动脉血管周围神经刺激中一氧化氮释放部位的比较研究”内皮。

Hisao Matsuda: "Involvement of cyclo-oxygenase-generated vasodilating eicosanoid(s) in addition to nitric oxide in endothelin-1-induced endothelium-dependent vasorelaxation in guinea pig aorta." Heart and Vessels. 8. (1993)

Hisao Matsuda：“除了一氧化氮之外，环加氧酶产生的血管舒张类二十烷酸也参与了豚鼠主动脉内皮素-1 诱导的内皮依赖性血管舒张作用。”

Hisao Matsuda et al.: "Involvement of cyclo-oxygenase generated vasodileting eicosanoid(s) in addition to nitric oxide in endothelin-1-induced endothelium-dependent vasorelaxation in guinea pig aorta" Heart and Vessels. Vol. 8 No. 3. 121-127 (1993)

Hisao Matsuda 等人：“在豚鼠主动脉内皮素-1 诱导的内皮依赖性血管舒张中，除一氧化氮外，环加氧酶的参与还产生了血管舒张类二十烷酸”《心脏和血管》。

Hisao Matsuda et al.: "Different modes of endothelin-1 action in pressor response in vivo and pulmonary parenchymal contraction in vitro in the guinea pig" Prostaglandins. Vol. 46 No. 6. 479-492 (1993)

Hisao Matsuda 等人：“豚鼠体内升压反应和体外肺实质收缩中内皮素 1 作用的不同模式”前列腺素。