Clinial Relevance of Novel Angiotensin II Generation Pathway within the Kidney

自从血管紧张素受体拮抗剂（AIIA）的发展以来，它就成为了ACE中争论的一个问题--我在AIIA中比在恢复再生疾病的进展中更有效。目前的研究是如何将血管紧张素吸收到ACE-I行动中的影响转化为什么，以及当非ACE-介导的血管紧张素第二代参与到这些代理商的再生保护中。Using intravital CCD相机技术， an angiotensin receptor antagonist （E4177） dilated different （AFF） and efferent arterioles （EFF）， in superficial nephrons （SP） and juxtamedullary nephrons （JM）。在某些情况下，硅氮普利拉在JM中进一步稀释了AFF和EFF，在SP中稀释了它只限于EFF。这些硅氮杂素诱导的挥发性和自然性已经被一个血管紧张素拮抗剂废除了。在与这些结果平行的情况下， Cilazaprilat增加了renal bradykinin的内容，在Cortex上比Medulla大。下一篇：血管紧张素II代通过ACE-mediat进行 ... More ED和非ACE介导的路径被测试了。ACE/非ACE介导的ANG II代的比率是8：2在狗的真实Cortex中，在心脏中证明了这一价值是4：6。在肾脏中，当与内部管理的ANG I和[Proy D111 YE D1，D-Alay D112 YE D1]-ANGI（S） （ANGI不能通过ACE转换为ANG II的模拟）上系统血压（BP）和循环血流（RBF）， S要求100-符合更高的情况，以获得BP和RBF相同程度的变化。进一步的研究使用室内针型CCD摄像机显微镜演示，其中线性的、有效果的、缩小的局部动作，并与ANGI的那些进行比较。S在RBF中服用100纳摩尔的剂量为30%，完全被GANG受体拮抗剂拒绝，但仅被Chymostatin抑制50%。最后，对慢性ACE的有效性进行了比较--I和ALA治疗是制作的。在与急性研究的对比下，不健康的血管紧张素内容几乎是相同的，从ACE-I-和AIIA治疗的狗。在反应性对血管紧张素的分化对血管紧张素水平和作用的分化对血管紧张素对ACE-I的分化的对血管紧张素的反应和有效的动脉紧张素对急性管理的反应中的局部异质性; ACE-I-增强的血管紧张素的作用将参与ACE-I的全球性血动力学变化。Futhermore，非ACE活动，与ACE活动比较，与再生ANG II一代的关系较少，以及青少年介导的ANG II一代只分享非ACE介导的ANG II生产的一半。慢性治疗，如何，失败，以证明ACE-I-诱导的肠梗阻蛋白累积在保护的放射性损伤中的益处。Less（低）

Since the development of angiotensin receptor antagonists (AIIA), it has been a matter of controversy whether ACE-I is more effective than AIIA in retarding the progression of renal disease. The present study was conducted to elucidate whether the accumulation of bradykinin contributes to the ACE-I action, and whether non-ACE-mediated angiotensin II generation participates in the renal protection of these agents. Using intravital CCD camera technique, an angiotensin receptor antagonist (E4177) dilated different (AFF) and efferent arterioles (EFF), in superficial nephrons (SP) and juxtamedullary nephrons (JM). Subsequently, cilazaprilat caused further dilation of both AFF and EFF in JM, whereas in SP it dilated only EFF. These cilazaprilat-induced vasodilation and natriuresis were abolished by a bradykinin antagonist. In parallel with these results, cilazaprilat increased renal bradykinin contents, greater in the medulla than in the cortex. Next, angiotensin II generation via ACE-mediat … More ed 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ィイD111ィエD1, D-AlaィイD112ィエD1]-ANGI (S) (an ANGI 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 ANGI. S at a dose of 100 nmol caused 30% decrements in RBF, which was completely abolished by g ANG receptor antagonist, but was only 50% inhibited by chymostatin. Finally, the comparison of the efficacy of chronic ACE-I and AllA treatment was made. In contrast to the acute study, intrarenal bradykinin contents were nearly the same in renal tissues from ACE-I-and AIIA-treated dogs. In conclusion, zonal heterogeneity in renal bradykinin levels and segmental differences in reactivity to bradykinin contribute to the diverse responsiveness of renal afferent and efferent arterioles to acute administration of ACE-I; ACE-I-enhanced kinin action would participate in glomerular hemodynamic changes by ACE-I. Futhermore, 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. Chronic treatment, however, fails to demonstrate the benefit of ACE-I-induced intrarenal bradykinin accumulation in protecting renal injury. Less