Effects of angiotensin-(1-7) blockade on renal function in rats with enhanced intrarenal Ang II activity
Effects of angiotensin-(1-7) blockade on renal function in rats with enhanced intrarenal Ang II activity
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DOI：
10.1111/j.1523-1755.2005.00222.x
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发表时间：
2005-04-01
影响因子：
19.6
通讯作者：
Cervenka, L
中科院分区：
文献类型：
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作者：
Bürgelová, M;Kramer, HJ;Cervenka, L
背景越来越多的证据表明，血管紧张素-（1-7）[Ang-（1-7）]在肾素-血管紧张素系统（RAS）被激活时作为Ang II的内源性拮抗剂发挥作用。因此，在本研究中，我们比较了急性肾内（i.r.）Ang-（1-7）受体阻断剂在正常和肾内Ang II浓度升高条件下对肾功能的影响。将充满盐的Hannover-Sprague道利大鼠（HanSD）作为对照动物。作为Ang II增强作用的模型，我们首先使用携带Ren-2肾素基因（TGR）的转基因大鼠，其次使用Ang II输注大鼠，第三使用正常盐摄入的双肾单夹（2K 1C）高血压大鼠，第四使用盐耗尽的TGR和HanSD。I.R. Ang-（1-7）受体阻断剂可显著降低2K 1C大鼠的肾小球滤过率（GFR）、肾血浆流量（RPF）和钠排泄量，并可降低去盐TGR和HanSD大鼠的钠排泄量。相比之下，I.R. Ang-（1-7）受体阻断剂对高盐TGR和HanSD以及Ang II灌注大鼠的GFR、RPF和钠排泄无显著影响。这些发现表明，在正常肾内RAS活性和通过输注Ang II或通过在充满盐的条件下插入肾素基因而增加肾内Ang II作用的条件下，Ang-（1-7）不是调节肾功能的重要因素。相反，在由于肾动脉夹闭或钠限制引起的内源性RAS激活的条件下，Ang-（1-7）充当Ang II的血管收缩作用的对手。
Background. Increasing evidence suggests that angiotensin-(1-7) [Ang-(1-7)] acts as an endogenous antagonist of Ang II when the renin-angiotensin system (RAS) is activated. In the present study, we therefore compared the effects of acute intrarenal (i.r.) Ang-(1-7) receptor blockade on renal function under conditions of normal and increased intrarenal Ang II concentration.Methods. Salt-replete Hannover-Sprague Dawley rats (HanSD) served as control animals. As models with enhanced action of Ang II we first used transgenic rats harboring the Ren-2 renin gene (TGR), second, Ang II-infused rats, third, 2-kidney, 1-clip (2K1C) hypertensive rats on normal salt intake, and fourth, salt-depleted TGR and HanSD.Results. I.r. Ang-(1-7) receptor blockade elicited significant decreases in glomerular filtration rate (GFR), renal plasma flow (RPF), and sodium excretion in 2K1C rats, and in salt-depleted TGR and HanSD. In contrast, i.r. Ang-(1-7) receptor blockade did not significantly change GFR, RPF, and sodium excretion in salt-replete TGR and HanSD, or in Ang II-infused rats.Conclusion. These findings suggest that under conditions of normal intrarenal RAS activity and increased intrarenal Ang II action by infusion of Ang II or by insertion of a renin gene in salt-replete conditions, Ang-(1-7) is not an important factor in the regulation of renal function. In contrast, under conditions of endogenous RAS activation due to clipping of the renal artery or to sodium restriction, Ang-(1-7) serves as opponent of the vasoconstrictor actions of Ang II.