Sutudy of vascular reactions in response to hemodynamic factors assessed by stretch activation

通过拉伸激活评估血流动力学因素的血管反应研究

• 批准号: 04671360
• 负责人: NAKAYAMA Koichi
• 金额: $ 1.34万
• 依托单位: Uuniversity of Shizuoka
• 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-04671360/
• 关键词: Cerebral and Coronary Artery; Biomechanics; Stretch; Stretch Activation; Mechanical Receptor; Vascontraction; Phopspholipase C; Ca^<2+> Signaling; 物理情報; 圧負荷; 筋原性収縮反応; アーテリオグラフ; モノクロタリン肺高血圧; Ca^<2+>チャネル

Cerebral and coronary arteries are extremely sensitive to hemodynamic factors, i.e., biomichacal stimule, including blood pressure and blood flow. I have investigated the ca^<2+>-signaling mechanisms of mechanical reception in the cardiovascular system from the following point of view, and as a leader i have promoted the progress of this relatively underdeveloped research field. I have regarded the myogenic contractile reaction of blood vessels in response to stretch of vascular wall or an increase in intraluminal pressure as a kind of cellular/intracellular and Ca^<2+> signaling ; and 3) the cross-bridge property of contractile elements. I could have showed interesting results as follows which will promise the future progress in the research. I have found that membrane fluidity strongly affects the sensitivity of a mechano-receptor site, and an amiloride-sensitive component, a possible stretch-activated channel, may play a role in the genesis of myogenic activity. In addition, the biomechanical stimulus augmented the activity of phospholipase C, production of inositol trisphosphate, and increase in cytosolic Ca^<2+> concentration, which indicates a possible role of GTP-binging proteins coupled with this enxyme in the transformation of mechanical stimulus to cellular signalings. Moreover, myogenic activity is found to be in-between the contraction produced by phorbol esters and high K^+ depolarizing stimulus in the property of cross-bridge cycling. These results suggest that vascular reaction in response to biomechanical stimuli is mediated through a novel mechanisum of cellular signaling.

脑动脉和冠状动脉对血液动力学因素极其敏感，即，生物机械刺激，包括血压和血流。我从以下角度研究了心血管系统机械感受的Ca^<2+>-信号机制，并作为领导者推动了这一相对欠发达的研究领域的进展。我认为血管响应血管壁拉伸或腔内压力增加的肌源性收缩反应是一种细胞内/细胞内和Ca^<2+>信号传导;以及3）收缩元件的跨桥特性。我本可以展示如下有趣的结果，这将预示着研究的未来进展。我发现，膜流动性强烈影响机械受体位点的敏感性，阿米洛利敏感成分，一种可能的牵张激活通道，可能在肌源性活动的发生中发挥作用。此外，生物力学刺激增强了磷脂酶C的活性、三磷酸肌醇的产生以及胞浆Ca^2+浓度的增加，这表明与该酶偶联的GTP结合蛋白在机械刺激转化为细胞信号中可能起作用。此外，生肌活性被发现介于佛波醇酯产生的收缩和高K^+去极化刺激之间，具有跨桥循环的性质。这些结果表明，血管对生物力学刺激的反应是通过一种新的细胞信号传导机制介导的。

项目成果

Nakayama,K.,Nozawa,Y.and Fukuta,Y.: "Allosteric interaction of semotiadil fumarate,a novel benzothiazine,with 1,4-dihydropyridines,phenylalkylamine,and 1,5-benzothiazepines at the Ca^<2+>-channel antagonist binding sites in canine skeletal muscle membrane

Nakayama, K.、Nozawa, Y. 和 Fukuta, Y.：“富马酸赛替地尔（一种新型苯并噻嗪）与 1,4-二氢吡啶、苯烷基胺和 1,5-苯并硫氮杂卓类药物在 Ca^2 > 通道上的变构相互作用

Nakayama,K.and Tanaka,Y.: "Specific signal transduction in the stretch-induced tone of vascular tissue.In:Resistance Arteries.Structure and Function.Ed.by M.J.Mulvany,C.Aalkjaer,A.M.Heagerty,N.C.B.Nyborg and S.Strandgaard." Elsevier Science Publishers B.V

Nakayama, K. 和 Tanaka, Y.：“血管组织拉伸诱导张力中的特定信号转导。见：阻力动脉。结构和功能。编辑：M.J.Mulvany、C.Aalkjaer、A.M.Heagerty、N.C.B.Nyborg 和 S

Koichi Nakayama, Shinzoh Hata, Hiromi Ishiro, Yoshio Tanaka and Kunio Ishii: "Potentiation by endothelin-1 of 5-hydroxytryptamineinduced contraction in coronary artery of the pig." Jpn.J.Pharmacol. 58(Suppl.2). 281 (1992)

Koichi Nakayama、Shizoh Hata、Hiromi Ishiro、Yoshio Tanaka 和 Kunio Ishii：“内皮素 1 增强 5-羟色胺诱导的猪冠状动脉收缩。”

Yoshio Tanaka, Shinzo Hata, Hiromi Ishiro, Kunio Ishii and Koichi Nakayama: "Stretching releases Ca^<2+> from intracellular sites in canine cerebral arteries." Can.J.Physiol.Pharmacol.in press. (1994)

Yoshio Tanaka、Shinzo Hata、Hiromi Ishiro、Kunio Ishii 和 Koichi Nakayama：“拉伸会从犬脑动脉的细胞内位点释放 Ca^<2>。”

Yoshio Tanaka, Hiromi Ishiro, Tohru Nakayama, Michihiro Saito, Kunio Ishii and Koichi Nakayama.: "Vasoconstrictory characteristics of endothelin-1 and neuropeptide Y in coronary and cerebral arteries and the effects of Ca^<2+> antagonistic vasodilators."

Yoshio Tanaka、Hiromi Ishiro、Tohru Nakayama、Michihiro Saito、Kunio Ishii 和 Koichi Nakayama.：“冠状动脉和脑动脉中内皮素-1 和神经肽 Y 的血管收缩特性以及 Ca^2 拮抗血管扩张剂的作用。”