IDENTIFICATION AND PATHOPHYSIOLOGICAL SIGNIFICANCE OF MYOENDOTHELIAL CAP JUNCTIONS

肌内皮帽连接的识别及其病理生理学意义

• 批准号: 13670722
• 负责人: FUJII Koji
• 金额: $ 1.54万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670722/
• 关键词: connexin; gap junction; angiotensin II; EDHF; hypertension; 内皮依存性過分極反応; 血管内皮細胞; 加齢; ラット

The present project was designed to determine the role of gap junctions in endothelium-derived hyperpolarizing factor (EDHF)-mediated vascular hyperpolarization, the types of connexins composing gap junctions, and the pathophysiological roles of vascular gap junctions.In the rat arteries, inhibitors of gap junctions markedly inhibited EDHF-mediated hyperpolarization, suggesting that gap junctions play an important role in EDHF-mediated hyperpolarization. Furthermore, immunohistochemical analysis revealed that, although connexins 37, 40 and 43 are expressed in the vascular wall, connexin 37 and 40 are the two major connexins expressed between endothelial cells, suggesting that these connexins may play a pivotal in the EDHF-mediated hyperpolarization.We have previously shown that EDHF-mediated hyperpolarization was impaired in arteries from aged rats. In this study, we demonstrated that antihypertensive treatment with angiotensin II receptor antagonist candesartan cillexetil prevented the age-related impairment of EDHF-mediated hyperpolarization.EDHF-mediated hyperpolarization was also impaired by hypertension, and anthihypertensive treatments corrected this abnormality. The present study evaluated the effects of hypertension and antihypertensive treatments on the expressions of connexins. We found that the expressions of connexin 37 and 40 in endothelial cells were significantly decreased in hypertension, and the antihypertensive treatment with candesartan cilexetil normalized the expressions of these connexins, findings consistent with those of EDHF-mediated hyperpolarization.These findings suggest that gap junctions (connexins 37 and 40) play an important role in the EDHF-mediated hyperpolarization, and the alterations of gap junction may be associated with changes of EDHF-mediated hyperpolarization under pathophysiological conditions, such as hypertension.

本研究旨在研究缝隙连接在内皮衍生超极化因子(EDHF)介导的血管超极化中的作用、缝隙连接蛋白的类型以及血管缝隙连接的病理生理作用。在大鼠动脉中，缝隙连接的抑制剂显著抑制EDHF介导的超极化，提示缝隙连接在EDHF介导的超极化中起重要作用。此外，免疫组织化学分析表明，尽管连接蛋白37、40和43在血管壁表达，但连接蛋白37和40是内皮细胞之间表达的两种主要连接蛋白，提示这些连接蛋白可能在EDHF介导的超极化中发挥关键作用。在这项研究中，我们证明了血管紧张素II受体拮抗剂坎地沙坦的降压治疗可以预防与年龄相关的EDHF介导的超极化的损害。EDHF介导的超极化也受到高血压的损害，降压治疗纠正了这种异常。本研究评价了高血压和降压治疗对连接蛋白表达的影响。我们发现高血压时内皮细胞连接蛋白37和40的表达显著降低，坎地沙坦降压治疗使这些连接蛋白的表达恢复正常，这一结果与EDHF介导的超极化的结果一致。这些结果表明缝隙连接(连接蛋白37和40)在EDHF介导的超极化中起重要作用，缝隙连接的改变可能与EDHF介导的超极化的变化有关。

项目成果

Kansui, Y., Fujii, K., Goto, K., Abe, I.: "Bradykinin enhances sympathetic neurotransmission in rat blood vessels."Hypertension. 39. 29-34 (2002)

Kansui, Y.、Fujii, K.、Goto, K.、Abe, I.：“缓激肽增强大鼠血管中的交感神经传递。”高血压。

Matsumura, K., Tsuchihasi, T., Fujii, K., Abe, I., Iida, M.: "Central ghrelin modulates sympathetic activity in conscious rabbits"Hypertension. 40・11. 694-699 (2002)

Matsumura, K.、Tschihasi, T.、Fujii, K.、Abe, I.、Iida, M.：“中枢饥饿素调节有意识的兔子的交感神经活动”高血压 40・11。

Kansui, Y., Fujii, K., Goto, K., Abe, I., Iida, M.: "Angiotension II receptor antagonist improves age-related endothelial dysfunction."J. Hypertens.. 20. 439-446 (2002)

Kansui, Y.、Fujii, K.、Goto, K.、Abe, I.、Iida, M.：“血管紧张素 II 受体拮抗剂可改善与年龄相关的内皮功能障碍。”J.

Kansui, Y., Fujii, K.., Goto, K., Abe, I.: "Bradykinin enhances sympathetic neurotransmission in rat blood vessels"Hypertension. 39・1. 29-34 (2002)

Kansui，Y.，Fujii，K..，Goto，K.，Abe，I.：“缓激肽增强大鼠血管中的交感神经传递”39・1（2002）。

Goto, K., Fujii, K., Abe, I., Fujishima, M.: "Impaired β-adrenergic hyperpolarization in arteries from prehypertensive spontaneously hypertensive rats"Hypertension. 37・2. 609-613 (2001)

Goto, K.、Fujii, K.、Abe, I.、Fujishima, M.：“高血压前期自发性高血压大鼠动脉β-肾上腺素能超极化受损”37・2 (2001)。