血管紧张素转换酶抑制AT1受体封锁修改pressure-natriuresis添加剂机制关系的老鼠与人类肾素和血管紧张肽原基因。

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总值Mervaala E, Dehmel B, V, Lippoldt, Bohlender J, Milia房颤,Ganten D,勒夫特足球俱乐部

血管紧张素转换酶抑制AT1受体封锁修改pressure-natriuresis添加剂机制关系的老鼠与人类肾素和血管紧张肽原基因。

J是Soc Nephrol。1999年8月,10 (8):1669 - 80。

PubMed ID

10446934 (在PubMed

]

文摘

intrarenal因素负责double-transgenic高血压大鼠(dTGR)窝藏人类肾素和血管紧张肽原基因尚不清楚。pressure-natriuresis和利尿的关系以应对慢性血管紧张素转换酶(ACE)抑制AT1受体封锁进行评估。肾肾素-血管紧张素和一氧化氮(NO)系统基因表达也被调查。六个dTGR治疗3周的轻快与高频剂量的cilazapril(10毫克/公斤,口头)或洛沙坦(10毫克/公斤,口头)或药物组合。在未经处理的dTGR, pressure-natriuresis关系被最大限度地向右移动了大约70到80毫米汞柱,肾血流量(RBF)和肾小球滤过率(GFR)明显下降。Submaximal cilazapril和洛沙坦剂量收缩压降低了30毫米汞柱,改变了pressure-natriuresis曲线左侧的25到30毫米汞柱。Cilazapril RBF增加和肾小球滤过率(GFR)值观察血压正常的控制动物,但没有明显影响部分钠排泄(FENa)或部分水排泄(FEH2O)曲线。相比之下,洛沙坦对RBF或肾小球滤过率(GFR)但没有显著的影响改变了FENa和FEH2O曲线左移。cilazapril和洛沙坦组合完全规范化的BP和转移pressure-natriuresis曲线左更比单独用药。当cilazapril和洛沙坦在高剂量管理(30毫克/公斤,口头),这两种药物同样改变了pressure-natriuresis曲线左,由50毫米汞柱。 Both drugs increased RBF and GFR; however, only losartan shifted FENa and FEH2O curves leftward. Human and rat renin and angiotensinogen genes were downregulated in dTGR and were increased by losartan and cilazapril treatments, whereas no changes in the expression of rat ACE and AT1A receptor genes were observed. Endothelial NO synthase expression was increased by cilazapril but not by losartan. Neither inducible NO synthase nor neural NO synthase gene expression was affected by drug treatments. Therefore, submaximal ACE inhibition enhanced sodium excretion mainly by increasing RBF and GFR, whereas submaximal AT1 receptor blockade decreased tubular sodium and water reabsorption. The combination of the two drugs produced an additive effect. The ACE inhibitor effects may involve increased endothelial NO synthase expression, perhaps related to the inhibition of bradykinin degradation.

DrugBank数据引用了这篇文章

药物靶点

药物	目标	类	生物	药理作用	行动
Cilazapril	血管紧张素转换酶	蛋白质	人类	是的	抑制剂	细节
Cilazaprilat	血管紧张素转换酶	蛋白质	人类	是的	不可用	细节