Differential regulation of angiotensin-(1-12) in plasma and cardiac tissue in response to bilateral nephrectomy
Differential regulation of angiotensin-(1-12) in plasma and cardiac tissue in response to bilateral nephrectomy
复制标题
DOI：
10.1152/ajpheart.01114.2008
复制
发表时间：
2009-04-01
影响因子：
4.8
通讯作者：
Sowers, James R.
中科院分区：
文献类型：
--
作者：
Ferrario, Carlos M.;Varagic, Jasmina;Sowers, James R.
Ferrario CM，Varagic J，Habibi J，Nagata S，Kato J，Chappell MC，Trask AJ，Kitamura K，Whaley-Connell A，Sowers JR.双侧肾切除术后血浆和心脏组织中血管紧张素-（1-12）的差异调节。美国生理学杂志心脏循环生理学296：H1184-H1192，2009年。首次发表于2009年2月13日; doi：10.1152/ajpheart. 01114.2008.-我们检测了48 h双侧肾切除术对成年Wistar-Kyoto大鼠血浆和心脏组织血管紧张素-（1- 12）[ANG-（1-12）]、ANG I和ANG II表达的影响，以评估去除肾肾素诱导的功能变化。目的是扩大ANG-（1-12）作为替代的非肾素依赖性血管紧张素形成底物的证据。肾切除术对循环和心脏血管紧张素产生不同的影响。与对照组相比，肾切除术后血浆ANG-（1-12）、ANG I和ANG II水平显著降低，同时心脏ANG-（1-12）、ANG I和ANG II浓度升高。肾切除术后血浆ANG-（1-12）下降34%，同时血浆ANG I和ANG II分别下降78%和66%（与对照组相比P < 0.05）。相比之下，无肾大鼠的心脏ANG（1-12）平均为276 +/- 24 fmol/mg，而对照组为144 +/- 20 fmol/mg（P < 0.005）。无肾大鼠心脏ANG I和ANG II值分别为300 +/- 15和62 +/- 7 fmol/mg，而对照组ANG I为172 +/- 8 fmol/mg，ANG II为42 +/- 4 fmol/mg（P < 0.001）。定量免疫荧光显示肾切除后WKY大鼠心脏组织血管紧张素原、ANG I、ANG II和AT（1）受体的平均灰度密度显著增加。心脏肾素染色微弱，肾切除术后无变化，与心脏肾素mRNA减少80%相关。这些变化伴随着p47（phox），Rac 1和Nox 4亚型表达的显着增加。总之，ANG-（1-12）可能是血管紧张素肽形成的功能性前体，在缺乏循环肾素。
Ferrario CM, Varagic J, Habibi J, Nagata S, Kato J, Chappell MC, Trask AJ, Kitamura K, Whaley-Connell A, Sowers JR. Differential regulation of angiotensin-(1-12) in plasma and cardiac tissue in response to bilateral nephrectomy. Am J Physiol Heart Circ Physiol 296: H1184-H1192, 2009. First published February 13, 2009; doi:10.1152/ajpheart. 01114.2008.-We examined the effects of 48 h bilateral nephrectomy on plasma and cardiac tissue expression of angiotensin-(1-12) [ANG-(1-12)], ANG I, and ANG II in adult Wistar-Kyoto rats to evaluate functional changes induced by removing renal renin. The goal was to expand the evidence of ANG-(1-12) being an alternate renin-independent, angiotensin-forming substrate. Nephrectomy yielded divergent effects on circulating and cardiac angiotensins. Significant decreases in plasma ANG-(1-12), ANG I, and ANG II levels postnephrectomy accompanied increases in cardiac ANG-(1-12), ANG I, and ANG II concentrations compared with controls. Plasma ANG-(1-12) decreased 34% following nephrectomy, which accompanied 78 and 66% decreases in plasma ANG I and ANG II, respectively (P < 0.05 vs. controls). Contrastingly, cardiac ANG( 1-12) in anephric rats averaged 276 +/- 24 fmol/mg compared with 144 +/- 20 fmol/mg in controls (P < 0.005). Cardiac ANG I and ANG II values were 300 +/- 15 and 62 +/- 7 fmol/mg, respectively, in anephric rats compared with 172 +/- 8 fmol/mg for ANG I and 42 +/- 4 fmol/mg for ANG II in controls (P < 0.001). Quantitative immunofluorescence revealed significant increases in average grayscale density for cardiac tissue angiotensinogen, ANG I, ANG II, and AT(1) receptors of WKY rats postnephrectomy. Faint staining of cardiac renin, unchanged by nephrectomy, was associated with an 80% decrease in cardiac renin mRNA. These changes were accompanied by significant increases in p47(phox), Rac1, and Nox4 isoform expression. In conclusion, ANG-(1-12) may be a functional precursor for angiotensin peptide formation in the absence of circulating renin.