Pathogenesis of renovascular hypertension with special reference to vascular protein synthesis

肾血管性高血压的发病机制，特别涉及血管蛋白合成

• 批准号: 10470332
• 负责人: NAKADA Teruhiro
• 金额: $ 7.1万
• 依托单位: YAMAGATA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 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-10470332/
• 关键词: Renovascular hypertension; vasscular contractile protein; Non-collagenous protein; Collagen; Sympathetic nerve; Norepinephrine; Captopril; Beta-aminopropionitrile; 腎血管性高血圧; 血管作動性物質; 線条体

Two-kidney-one, one-clip (2K-1C) rats were treated with splan-chnicotomy, beta-aminopropionitrile (collagen inhibitor), or captopril (angiotensin converting enzyme inhibitor) in the acute or chronic hypertensive phase. 3H-proline was injected into rats, and incorporation of 3H-proline into vascular collagen, non-collagenous protein and elastin were counted. The plasma level of the renin-angiotensin (R-A) system was assayed. In the acute phase of 2K-1C hypertensive rats whose R-A system was enhanced, captopril treatment further enhanced PRA and angiotensin I and suppressed angiotensin II while reducing blood pressure. Synthesis of the vascular protein was almost identical.In the chronic phase of 2K-1C hypertensive rats whose R-A system was within normal limits, increased incorporation rates of 3H-proline into non-collagenous protein or collagen of mesenteric arteries were decreased by splanchnicotomy or beta-aminopropionitrile and hypertension was lowered. Captopril failed to reduce pro … More tein synthesis. Thus, an enhanced R-A system participates in the pathogenesis of the acute phase of 2K-1C hypertension while increased non-collagenous protein and collagen syntheses of small arteries appear to play some role in the etiology of chronic phase of hypertension. In another experiment, high level of monoamines, such as dopamine (DA), DPAC and HVA enhanced synpathetic nerve system which resulted in hypertension in acute phase of 2K-1C, but not in chronic phase of 2K-1C.In clinical study we analyzed 99 patients with renovascular hypertension. Evidence has been presented that : (1) for patients with fibromuscular dysplasia and those with aortitis the mean age of cured patients was younger than non-cured patients and the preoperative hypertensive period of the former patients was shorter than the latter patients, but as for the patients with atherosclerosis, there were no significant differences in these variables among cured, alleviative and non-cured groups, (2) for the affected renal arteries, lesions of bilateral renal artery and aorta or lesions located at extrarenal and intrarenal arteries were difficult to be cured in any histological vascular forms, (3) for the patients with fibromuscular dysplasia, improvement of hypertension was achieved more frequently than those with atherosclerosclerosis. Similar result was obtained in the upright posture test in lesser extent, but a almost useless in patients with aortitis.These results indicate that enhenced R-A system still appears to play some role for sustaining hypertension in patients with fibromuscular dysplasia and those with atherosclerosis, but other factors responsible for maintenance of hypertension must be considered in patients with aortitits whose preoperative hypertensive period is long. Less

两肾一夹（2K-1C）大鼠在急性或慢性高血压期分别接受胰切开术、β -氨基丙腈（胶原抑制剂）或卡托普利（血管紧张素转换酶抑制剂）治疗。给大鼠注射3h -脯氨酸，计数3h -脯氨酸与血管胶原、非胶原蛋白和弹性蛋白的掺入量。测定肾素-血管紧张素（R-A）系统血浆水平。在R-A系统增强的2K-1C高血压大鼠急性期，卡托普利治疗在降低血压的同时进一步增强PRA和血管紧张素I，抑制血管紧张素II。血管蛋白的合成几乎完全相同。在R-A系统正常的2K-1C高血压大鼠慢性期，开腹或-氨基丙腈可降低3h -脯氨酸与肠系膜动脉非胶原蛋白或胶原蛋白的掺入率，降低高血压。卡托普利没能减少蛋白质的合成。因此，R-A系统的增强参与了2K-1C高血压急性期的发病机制，而小动脉非胶原蛋白和胶原合成的增加似乎在高血压慢年期的病因学中起一定作用。在另一项实验中，多巴胺（DA）、DPAC和HVA等单胺类物质的高水平增强了交感神经系统，导致2K-1C急性期高血压，但在慢慢性期没有高血压。在临床研究中，我们分析了99例肾血管性高血压患者。有证据表明：(1)纤维肌肉发育不良患者和主动脉炎患者，治愈患者的平均年龄小于未治愈患者，且前者术前高血压期短于后者，而动脉粥样硬化患者，治愈组、缓解组和未治愈组在这些变量上无显著差异；双侧肾动脉、主动脉病变或位于肾外、肾内动脉病变在任何组织学血管形态下都难以治愈。(3)纤维肌肉发育不良患者高血压的改善频率高于动脉粥样硬化患者。在直立姿势测试中获得的相似结果在较小程度上，但在主动脉炎患者中几乎无用。这些结果表明，增强的R-A系统对纤维肌肉发育不良患者和动脉粥样硬化患者的高血压维持仍有一定作用，但对于术前高血压期较长的主动脉炎患者，必须考虑其他因素对高血压维持的影响。少

项目成果

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中田 瑛浩: "新 図説泌尿器科学講座"メディカルビュー社. 365 (1199)

Eihiro Nakata：《泌尿外科新图解课程》医学观点出版 365 (1199)。

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Tomaru M.and Nakada T.: "Low level of urinary kallirein in the development of adrenal-regeneration hypertension"Yamagata Medical Journal. 16. 35-46 (1998)

Tomaru M.和Nakada T.：“肾上腺再生性高血压发生过程中尿激肽水平低”山形医学杂志。

都丸政彦: "Low level of urinary kallikrein in the development of adrenal-regeneration hypertension" Yamagata Med J. 16・2. 35-46 (1998)

Masahiko Tomaru：“肾上腺再生性高血压的尿激肽释放酶水平低” Yamagata Med J. 16・2 (1998)。