Cervenka L, Wang C T, Mitchell K D, Navar L G
Department of Physiology, Tulane University School of Medicine, New Orleans, LA, USA.
Hypertension. 1999 Jan;33(1):102-7. doi: 10.1161/01.hyp.33.1.102.
-Previous studies have shown that whereas the nonclipped kidney in two-kidney, one clip (2K1C) rats undergoes marked depletion of renin content and renin mRNA, intrarenal angiotensin II (Ang II) levels are not suppressed; however, the distribution and functional consequences of intrarenal Ang II remain unclear. The present study was performed to assess the plasma, kidney, and proximal tubular fluid levels of Ang II and the renal responses to intrarenal Ang II blockade in the nonclipped kidneys of rats clipped for 3 weeks. The Ang II concentrations in proximal tubular fluid averaged 9.19+/-1.06 pmol/mL, whereas plasma Ang II levels averaged 483+/-55 fmol/mL and kidney Ang II content averaged 650+/-66 fmol/g. Thus, as found in kidneys from normal rats with normal renin levels, proximal tubular fluid concentrations of Ang II are in the nanomolar range. To avoid the confounding effects of decreases in mean arterial pressure (MAP), we administered the nonsurmountable AT1 receptor antagonist candesartan directly into the renal artery of nonclipped kidneys (n=10). The dose of candesartan (0.5 microg) did not significantly decrease MAP in 2K1C rats (152+/-3 versus 148+/-3 mm Hg), but effectively prevented the renal vasoconstriction elicited by an intra-arterial bolus of Ang II (2 ng). Candesartan elicited significant increases in glomerular filtration rate (GFR) (0.65+/-0. 06 to 0.83+/-0.11 mL. min-1. g-1) and renal blood flow (6.3+/-0.7 to 7.3+/-0.9 mL. min-1. g-1), and proportionately greater increases in absolute sodium excretion (0.23+/-0.07 to 1.13+/-0.34 micromol. min-1. g-1) and fractional sodium excretion (0.38+/-0.1% to 1.22+/-0. 35%) in 2K1C hypertensive rats. These results show that proximal tubular fluid concentrations of Ang II are in the nanomolar range and are much higher than can be explained on the basis of plasma levels. Further, the data show that the intratubular levels of Ang II in the nonclipped kidneys of 2K1C rats remain at levels found in kidneys with normal renin content and could be exerting effects to suppress renal hemodynamic and glomerular function and to enhance tubular reabsorption rate.
-以往研究表明，在两肾一夹（2K1C）大鼠中，未夹闭的肾脏肾素含量和肾素mRNA显著减少，而肾内血管紧张素II（Ang II）水平并未受到抑制；然而，肾内Ang II的分布及功能后果仍不清楚。本研究旨在评估大鼠夹闭3周后未夹闭肾脏中Ang II的血浆、肾脏及近端肾小管液水平，以及肾内Ang II阻断后的肾脏反应。近端肾小管液中Ang II浓度平均为9.19±1.06 pmol/mL，而血浆Ang II水平平均为483±55 fmol/mL，肾脏Ang II含量平均为650±66 fmol/g。因此，如同在肾素水平正常的正常大鼠肾脏中所发现的那样，近端肾小管液中Ang II浓度处于纳摩尔范围。为避免平均动脉压（MAP）降低的混杂效应，我们将不可逾越的AT1受体拮抗剂坎地沙坦直接注入未夹闭肾脏的肾动脉（n = 10）。坎地沙坦剂量（0.5μg）在2K1C大鼠中未显著降低MAP（152±3对148±3 mmHg），但有效预防了动脉内推注Ang II（2 ng）引起的肾血管收缩。坎地沙坦使2K1C高血压大鼠的肾小球滤过率（GFR）显著增加（从0.65±0.06至0.83±0.11 mL·min-1·g-1）和肾血流量增加（从6.3±0.7至7.3±0.9 mL·min-1·g-1），并且绝对钠排泄（从0.23±0.07至1.13±0.34 μmol·min-1·g-1）和钠排泄分数（从0.38±0.1%至1.22±0.35%）成比例地更大增加。这些结果表明，近端肾小管液中Ang II浓度处于纳摩尔范围，且远高于基于血浆水平所能解释的浓度。此外，数据表明2K1C大鼠未夹闭肾脏中肾小管内Ang II水平维持在肾素含量正常的肾脏中所发现的水平，并可能正在发挥作用以抑制肾血流动力学和肾小球功能，并提高肾小管重吸收率。
