Komlosi Peter, Fuson Amanda L, Fintha Attila, Peti-Peterdi János, Rosivall Laszlo, Warnock David G, Bell Phillip Darwin
Department of Medicine, Division of Nephrology, University of Alabama at Birmingham, USA.
Hypertension. 2003 Aug;42(2):195-9. doi: 10.1161/01.HYP.0000081221.36703.01. Epub 2003 Jun 30.
Angiotensin (Ang) II directly stimulates epithelial sodium channel activity in the rabbit cortical collecting duct. Because Ang I and converting enzyme analogues might be present in the distal nephron, this raises the possibility of intraluminal generation of Ang II. Conversion of Ang I to Ang II was monitored by Ang II-dependent changes in intracellular sodium concentration as a reflection of sodium transport across the apical membrane. This involved imaging-based fluorescence microscopy with sodium-binding benzofuran isophthalate in isolated, perfused, cortical collecting-duct segments from rabbit kidney. Principal and intercalated cells were differentiated by rhodamine-conjugated peanut lectin. Control principal cell intracellular sodium concentration, during perfusion with 25 mmol/L NaCl and zero sodium in the bath plus monensin (10(-5) mol/L) averaged 5.8+/-0.14 mmol/L (n=156). The increase in intracellular sodium concentration, when luminal NaCl was increased from 25 to 150 mmol/L, was elevated by 3.5-fold in the presence of intraluminal Ang I (10(-6) mol/L). Also, the effects of Ang I on sodium transport were not significantly different from the effects of Ang II (10(-9) mol/L). Ang I was used in micromolar concentrations to ensure that there was sufficient substrate available for conversion to Ang II. Inhibition of the angiotensin-converting enzyme with captopril reduced the stimulatory effect of Ang I. These results suggest that intraluminal conversion of Ang I to Ang II can occur in the cortical collecting duct, resulting in enhanced apical sodium entry.
血管紧张素（Ang）II可直接刺激兔皮质集合管中的上皮钠通道活性。由于远曲小管中可能存在血管紧张素I（Ang I）和转化酶类似物，这就增加了管腔内生成Ang II的可能性。通过细胞内钠浓度的Ang II依赖性变化来监测Ang I向Ang II的转化，以此反映钠跨顶膜的转运情况。这涉及使用钠结合苯并呋喃异酞酸酯进行基于成像的荧光显微镜检查，所用材料为分离、灌注的兔肾皮质集合管节段。通过罗丹明偶联的花生凝集素来区分主细胞和闰细胞。在用25 mmol/L氯化钠灌注且浴液中钠浓度为零并添加莫能菌素（10⁻⁵ mol/L）的情况下，对照主细胞的细胞内钠浓度平均为5.8±0.14 mmol/L（n = 156）。当管腔内氯化钠浓度从25 mmol/L增加到150 mmol/L时，在管腔内存在Ang I（10⁻⁶ mol/L）的情况下，细胞内钠浓度的增加提高了3.5倍。此外，Ang I对钠转运的作用与Ang II（10⁻⁹ mol/L）的作用无显著差异。使用微摩尔浓度的Ang I以确保有足够的底物可转化为Ang II。用卡托普利抑制血管紧张素转换酶可降低Ang I的刺激作用。这些结果表明，在皮质集合管中可发生Ang I向Ang II的管腔内转化，从而导致顶膜钠内流增强。
