Clinical Relevance of Novel Angiotensin II Generation Pathway within the Kidney

肾脏内新型血管紧张素 II 生成途径的临床相关性

基本信息

批准号：
09470240
负责人：
SARUTA Takao
金额：
$ 4.16万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470240/
关键词：
chymase angiotensin kidney afferent arterioles efferent arterioles renal hemodynamics dexamethasone microscopy

项目摘要

Although angiotensin converting enzyme (ACE) inhibitors retard the progression of renal diseases, it remains undetermined whether a non-ACE-mediated pathway contributes to the angiotensin (ANG) ii generation within the kidney This study attempted to clarify the role of ACE and non-ACE pathway, including chymase, for ANG II generation within the kidney. ANG II generation via ACE-mediated and non-ACE-mediated pathways was examined. The ratio of ACE/non-ACE-mediated ANG II generation was 8 : 2 in dog renal cortex, whereas in the heart this value proved to be 4 : 6. In the kidney, when compared with the effects of intrarenally administered ANG I and [Pro^<11>, D-Ala^<12>]-ANG I (S) (an ANG I analog that cannot be converted to ANG II by ACE) on systemic blood pressure (BP) and renal blood flow (RBF), S required 100-fold higher concentrations to obtain the same degree of changes in BP and RBF.Further studies using intravital needle-type CCD camera microscopy demonstrated that renal afferent and efferent arteriolar actions of S were diminished, compared with those of ANG I.S at a dose of 100 nmol caused 30% decrements in RBF, which was completely abolished by an ANG receptor antagonist, but was only 50% inhibited by chymostatin. Finally, unlike systemic vascular beds, dexamethasone dilates the renal vasculature, which is associated with a decrease in renal interstitial ANG II formation and the paralleled inhibition of renal ACE activity, suggesting glucocorticoid does not affect non-ACE-mediated ANG II generation. Collectively, non-ACE activity, compared with ACE activity, contributes less to the renal ANG II generation, and chymase-mediated ANG II generation shares only half of the non-ACE-mediated ANG II production. Furthermore, non-ACE pathway does not play an important role in ANG II formation in glucocorticoid-treated kidneys Nevertheless, further studies are required to establish the role of non-ACE-mediated renal ANG II formation under a variety of renal diseases.

尽管血管紧张素转化酶（ACE）抑制剂阻碍了肾脏疾病的进展，但仍未确定是否有非ACE介导的途径是否有助于肾脏中的血管紧张素（ANG）II产生，这项研究试图澄清ACE和非ACE途径的作用，包括Ang II，包括Ang II，ac genney genne nekne for Ang II的生成。通过ACE II通过ACE介导的和非ACE介导的途径产生。 The ratio of ACE/non-ACE-mediated ANG II generation was 8 : 2 in dog renal cortex, whereas in the heart this value proved to be 4 : 6. In the kidney, when compared with the effects of intrarenally administered ANG I and [Pro^<11>, D-Ala^<12>]-ANG I (S) (an ANG I analog that cannot be converted to ANG II by ACE) on systemic blood pressure (BP) and renal blood流量（RBF），S需要更高浓度才能获得BP和RBF的相同程度的变化。使用室内针型CCD CCD摄像机显微镜进行研究表明，S ANG的肾脏降低了，与100 nmol降低了SAN的肾脏传染性和效率的小动物作用相比，S an an vandy sagror sagror sagror savers y i.s完全降低了30％的vers，这是rbf的30％降低的，这是RBF的30％降低的，这是rbf的30％降低。 50％抑制瓜瘤素。最后，与全身性血管床不同，地塞米松扩张了肾血管，这与肾脏间质ANG II形成的降低以及平行抑制肾ACE活性有关，这表明糖皮质激素不会影响非ACE ACE介导的ANG II产生。总体而言，与ACE活性相比，非ACE活性对肾脏ANG II的产生贡献较小，而Chymase介导的ANG II产生仅占非ACE介导的ANG II产生的一半。此外，非ACE途径在糖皮质激素治疗的肾脏中的ANG II形成中并不发挥重要作用，但仍需要进一步的研究来确定各种肾脏疾病下非ACE介导的肾ANG II形成的作用。