Renin increments the inward calcium current in the failing heart.
Renin increments the inward calcium current in the failing heart.
复制标题
肾素增加衰竭心脏中的内向钙电流。
DOI：
10.1097/01.hjh.0000226209.88312.db
复制
发表时间：
2006
期刊：
影响因子：
--
通讯作者：
DeMello,WalmorC
中科院分区：
文献类型：
--
作者：
DeMello,WalmorC
研究背景已有证据表明，心脏重构过程中涉及到肾素-血管紧张素系统的激活。在衰竭的心脏中，肾素是否能改变内向钙电流（ICa）尚不清楚。方法从4月龄心肌病仓鼠心室分离心肌细胞，采用膜片钳技术在全细胞构型下测量L-型I Ca。（128 pmol Ang I/ml/min）+血管紧张素原（110 pmol血管紧张素I产生的肾素耗尽）增加峰值ICa密度显着，马来酸依那普利抑制的作用（10 - 8 mol/l）或洛沙坦（10 - 7 mol/l）加入到浴中，表明肾素加血管紧张素原的作用与血管紧张素I的形成及其在血管紧张素II的转化有关。表面细胞膜。由于细胞内肾素透析，（128 pmol Ang I/ml/min）+血管紧张素原（110 pmol血管紧张素I产生的肾素耗尽）也增加峰值ICa密度显着，一种被细胞内氯沙坦抑制的效应（10− 8 mol/l），但不通过细胞外氯沙坦（10− 7 mol/l）结论细胞外肾素和血管紧张素原可通过在心肌细胞内形成钙通道而增加心肌细胞的ICa。血管紧张素II和激活血管紧张素1型受体在细胞膜表面。在细胞内给予肾素加血管紧张素原也可使ICa增加。这一发现可能表明，在衰竭的心脏中，肾素内化参与了内向钙电流的控制。
BackgroundEvidence is available that activation of the renin–angiotensin system is involved in cardiac remodeling. It is unknown whether renin can change the inward calcium current (I Ca) in the failing heart. This problem was investigated in the present study.MethodsCardiomyocytes were isolated from the ventricle of 4-month-old cardiomyopathic hamsters and measurements of the L-type I Ca were performed using the patch-clamp technique in a whole-cell configuration.ResultsExtracellular renin (128 pmol Ang I/ml per min) plus angiotensinogen (110 pmol angiotensin I generated by renin to exhaustion) incremented the peak I Ca density significantly, an effect suppressed by enalapril maleate (10− 8 mol/l) or by losartan (10− 7 mol/l) added to the bath, indicating that the effect of renin plus angiotensinogen was related to the formation of angiotensin I and its conversion to angiotensin II at the surface cell membrane. Renin internalization seems to increment the I Ca because intracellular dialysis of renin (128 pmol Ang I/ml per min) plus angiotensinogen (110 pmol angiotensin I generated by renin to exhaustion) also increased the peak I Ca density significantly, an effect suppressed by intracellular losartan (10− 8 mol/l) but not by extracellular losartan (10− 7 mol/l).ConclusionsExtracellular renin plus angiotensinogen increases the I Ca in isolated myocytes from the failing heart of cardiomyopathic hamsters through the formation of angiotensin II and the activation of angiotensin type 1 receptors at the surface cell membrane. A similar increment of I Ca was found with intracellular administration of renin plus angiotensinogen. This finding might indicate that renin internalization is involved in control of inward calcium current in the failing heart.