A PHARMACOLOGICAL STUDY ON THE DEVELOPMENT OF VASCULAR FUNCTIONAL DISORDER DURING VASCULAR REMODELING

血管重塑过程中血管功能障碍发生的药理学研究

• 批准号: 07670829
• 负责人: MATSUDA Hisao
• 金额: $ 1.54万
• 依托单位: NATIONAL CARDIOVASCULAR CENTER RESEARCH INSTITUTE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670829/
• 关键词: JNJURED VESSELS; NEUROEFFECTOR-ENDOTHELIAL INTERACTION; ADRENERGIC CONTRACTION; NITRIC OXIDE; 15-HYDROPEROXYEICOSATETRAENOIC ACID; SENSORY NEUROPEPTIDES; ENDOTHELIN; ENDOTHELIAL THICKENING; バルーン・カテーテル; 血小板活性化因子; 炎症性サイトカイン; 15-リポキシゲナーゼ; カルシトニン遺

This study investigate (1) pharmaco-physiological vasoactive properties of the autacoids possibly acting in injured vessels, and (2) altered adrenergic neurotransmission in these vessels.With respect to the former part, vasoactive properties of 15-hydroperoxyeicosatetraenoic acid and sensory neuropeptides were studied in relation to endothelial function. As a result, 15-hydroperoxyeicosatetraenoic acid induced both endothelium-dependent vasorelaxation and vasoconstriction which were dependent upon the concentration and the source of the studied vessels. Additionally, sensory neuropeptides, other principal mediators of neuroeffector-endothelial interaction, also showed different modes of vasorelaxation, endothelial nitric oxide-mediated or direct vasorelaxation, which were dependent upon the preparations, arteries or veins. Moreover, this study investigated the effects of endothelins on vascular adrenergic contraction. Endothelins augmented vascular adrenergic contraction via ET_A recep … More tors.The latter part of the present study investigated altered modulation of adrenergic contraction (AC) in injured muscular artery. Microballoon-injured guinea pig femoral artery (FA) served as material. Nitric oxide synthetase inhibitor significantly augmented AC in both control and injured FA.The degree of the augmentation was significantly attenuated in injured FA,compared with control FA.And so was acetylcholine-induced relaxation after noradrenaline precontraction. Morphologically, progressive endothelial thickening was observed in injured FA.These results indicate that attenuated inhibition of AC with nitric oxide, accompanied by endothelial thickening, could increase vascular tone in injured muscular artery. To further elucidate the mechanism of altered neuroeffector-endothelial interaction in injured artery, effects of platelet-activating factor on vascular AC was studied and this factor was shown to sugment AC via cyclo-oxygenase-generated eicosanoid (s) in an endothelium-dependent manner. Effects of proinflammatory cytokines are also being studied. Less

本研究探讨了（1）可能作用于受损血管的自他类物质的药理生理学血管活性特性和（2）这些血管中肾上腺素能神经传递的改变。关于前一部分，研究了15-氢过氧二十碳四烯酸和感觉神经肽的血管活性特性与内皮功能的关系。其结果是，15-hydroperoxyeicosatetraenoic酸诱导内皮依赖性血管舒张和血管收缩，这是依赖于浓度和所研究的血管的来源。此外，感觉神经肽，神经效应器-内皮相互作用的其他主要介质，也表现出不同的血管舒张模式，内皮一氧化氮介导的或直接的血管舒张，这取决于制剂，动脉或静脉。此外，本研究还探讨了内皮素对血管肾上腺素能收缩的影响。内皮素通过ET_A受体增强血管肾上腺素能收缩 ...更多信息 本研究的后半部分研究了损伤的肌肉动脉中肾上腺素能收缩（AC）的改变调制。以微球囊损伤的豚鼠股动脉为材料。一氧化氮合成酶抑制剂显著增加对照组和损伤组FA的AC，但损伤组AC增加的程度明显减弱，去甲肾上腺素预收缩后乙酰胆碱引起的AC松弛也明显减弱。形态学上，进行性内皮增厚观察损伤FA。这些结果表明，衰减抑制AC与一氧化氮，伴随着内皮增厚，可以增加血管紧张度损伤肌动脉。为了进一步阐明损伤动脉中神经效应物-内皮相互作用改变的机制，研究了血小板活化因子对血管AC的影响，并且该因子显示以内皮依赖性方式通过环氧合酶产生的类二十烷酸来维持AC。促炎细胞因子的作用也正在研究中。少

项目成果

Hisao Matsuda: "Different modes of sensory neuropeptides and nitric oxide involvement in relaxation of guinea-pig vessels" Journal of Autonomic Nervous System. 55. 115-122 (1995)

Hisao Matsuda：“感觉神经肽和一氧化氮参与豚鼠血管松弛的不同模式”自主神经系统杂志。

Hisao Matsuda et al.: "Different modes of sensory neuropeptides and nitric oxide involvement in relaxation of guinea-pig vessels" Journal of the Autonomic Nervous System. Vol.55, No.1-2. 115-122 (1995)

Hisao Matsuda 等人：“感觉神经肽和一氧化氮参与豚鼠血管松弛的不同模式”《自主神经系统杂志》。

Hisao Matsuda et al.: "Pharmacodynamics of 15 (S)-hydroperoxyeicosatetraenoic (15-HPETE) and 15 (S)-hydroxyeicosatetraenoic acid (15-HETE), in isolated arteries from guinea pig, rabbit, rat and human" Journal of Pharmacology and Experimental Therapeutics.

Hisao Matsuda 等人：“15 (S)-氢过氧二十碳四烯酸 (15-HPETE) 和 15 (S)-羟基二十碳四烯酸 (15-HETE) 在豚鼠、兔子、大鼠和人类离体动脉中的药效学”药理学杂志

Hisao Matsuda: "Different modes of sensory neuropeptides and nitric oxide involvement in relaxation of guinea-pig vessels." Journal of the Autonomic Nervous System. 55. 115-122 (1995)

Hisao Matsuda：“感觉神经肽和一氧化氮的不同模式参与豚鼠血管的松弛。”

Hisao Matsuda: "Pharmacodynamics of 15(S)-hydroperoxyeicosatetraenoic (15-HPETE) and 15 (S)-hydroxy-eicosatetraenoic acid (15-HETE) in isolated arteries from guiea pig,rabbit,rat and human" Journal of Pharmacology and Experimental Therapcutics. 273. 1182-

Hisao Matsuda：“15(S)-氢过氧二十碳四烯酸 (15-HPETE) 和 15(S)-羟基-二十碳四烯酸 (15-HETE) 在豚鼠、兔、大鼠和人离体动脉中的药效学”药理学与实验杂志