Microvascular endothelial control of bone metabolism in rats: nitric oxide and endothelin systems

大鼠骨代谢的微血管内皮控制：一氧化氮和内皮素系统

• 批准号: 10670713
• 负责人: TSUKAHARA Hirokazu
• 金额: $ 1.66万
• 依托单位: Fukui Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670713/
• 关键词: nitric oxide; endothelin; vascular endothelium; bone metabolism; metabolic bone disease; redox; ラット; 骨組織; 微小血管内皮細胞

The following is the summary of my current research project.1. Role of endothelin/endothelin receptor subtype A system in the control of bone metabolism (Reference #3)We found that the long-term blockade of the endothelin A receptor reduces bone formation and induces osteopenia in growing rats. This result suggests that endothelin produced by vascular endothelial cells plays an important role in bone growth and metabolism in vivo.2. Redox modulation of vascular endothelial cell function (Reference #4. 6, 7)Using the electrical cell-substrate impedance sensor technique, we observed that nitric oxide (NO) modulates cell-matrix and/or cell-cell adhesion in human microvascular endothelial cells and suggested that NO might modify microvascular permeability in humans. We also found the importance of the constitutive NO synthase activity in the maintenance of oxidant buffering capacity in rats.3. Pathophysiology of endothelial cell dysfunction (Reference #5)We have summarized our recent observations implicating insufficient NO production in pathological states (e.g., atherosclerosis, hypertension and heart failure) in the inappropriate response to angiogenic stimuli.4. Assessment of bone metabolism in infantile metabolic bone diseasesWe demonstrated for the first time that the low bone turnover state lies in the infantile osteopenia imperfecta type3.

以下是我目前研究项目的总结。内皮素/内皮素受体A亚型系统在骨代谢调控中的作用(参考文献3)我们发现，长期阻断内皮素A受体会减少生长期大鼠的骨形成，并导致骨量减少。这一结果提示，血管内皮细胞产生的内皮素在活体骨生长和代谢中起重要作用。血管内皮细胞功能的氧化还原调节(参考文献#4.6，7)利用电子细胞-底物阻抗传感器技术，我们观察到一氧化氮(NO)调节人微血管内皮细胞的细胞-基质和/或细胞-细胞黏附，提示NO可能改变人的微血管通透性。我们还发现，结构性一氧化氮合酶活性在维持大鼠氧化缓冲能力方面具有重要意义。内皮细胞功能障碍的病理生理学(参考文献#5)我们总结了我们最近的观察结果，即在病理状态(如动脉粥样硬化、高血压和心力衰竭)中，NO的产生不足导致对血管生成刺激的不适当反应。婴幼儿代谢性骨病的骨代谢评估我们首次证实，婴幼儿不完全性骨量减少3型存在骨转换低的状态。

项目成果

Tsukahara H, et al.: "Increased oxidative stress in rats with chronic nitric oxide depletion : Measurement of urinary 8-OHdG excretion"Redox Report. (印刷中). (2000)

Tsukahara H 等人：“慢性一氧化氮耗竭大鼠的氧化应激增加：尿 8-OHdG 排泄的测量”Redox 报告（2000 年出版）。

Tsukahara H, Hori C, Tsuchida S, Hiraoka M, Fujisawa K, Mayumi M.: "Role of endothelin in erythropoietin-induced hypertension."Nephron. 79. 499-500 (1998)

Tsukahara H、Hori C、Tsuchida S、Hiraoka M、Fujisawa K、Mayumi M.：“内皮素在促红细胞生成素诱发的高血压中的作用。”肾单位。

Tsukahara H, Ishida T, Mayumi M.: "Gas-phase oxidation of nitric oxide: Chemical kinetics and rate constant."Nitric Oxide: Biology and Chemistry. 3. 191-198 (1999)

Tsukahara H、Ishida T、Mayumi M.：“一氧化氮的气相氧化：化学动力学和速率常数。”一氧化氮：生物学和化学。

Tsukahara H, Noiri E, Jiang MZ, Hiraoka M, Mayumi M.: "Role of nitric oxide in human pulmonary microvascular endothelial adhesion."Life Sci. (in press). (2000)

Tsukahara H、Noiri E、Jiang MZ、Hiraoka M、Mayumi M.：“一氧化氮在人肺微血管内皮粘附中的作用。”生命科学。

Goligorsky MS, et al.: "Cooperation between endothelin and nitric oxide in promoting endothelial cell migration and angiogenesis"Clin Exp Pharmacol Physiol. 26. 269-271 (1999)

Goligorsky MS 等人：“内皮素和一氧化氮在促进内皮细胞迁移和血管生成中的合作”Clin Exp Pharmacol Physiol。