Angiotensin I conversion to angiotensin II stimulates cortical collecting duct sodium transport
Angiotensin I conversion to angiotensin II stimulates cortical collecting duct sodium transport
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DOI：
10.1161/01.hyp.0000081221.36703.01
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发表时间：
2003-08-01
期刊：
影响因子：
8.3
通讯作者：
Bell, PD
中科院分区：
文献类型：
--
作者：
Komlosi, P;Fuson, AL;Bell, PD
血管紧张素（Ang）II直接刺激兔皮质集合管上皮钠通道活性。由于血管紧张素I和转换酶类似物可能存在于远端肾单位，这提高了血管紧张素II的腔内生成的可能性。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，所述细胞内钠浓度的变化反映了跨顶膜的钠转运。这涉及基于成像的荧光显微镜与钠结合苯并呋喃双乙酸酯在离体，灌注，皮质集合管段从兔肾。用罗丹明标记的花生凝集素对主细胞和闰细胞进行分化。对照主细胞内钠浓度，在25 mmol/L NaCl和无钠浴加莫能菌素（10（-5）mol/L）灌注期间平均为5.8 +/- 0.14 mmol/L（n = 156）。当腔内NaCl浓度从25 mmol/L增加到150 mmol/L时，细胞内钠浓度的增加在腔内Ang I（10（-6）mol/L）存在下升高3.5倍。Ang I对钠转运的影响与Ang II（10（-9）mol/L）无显著性差异。以微摩尔浓度使用Ang I以确保有足够的底物可用于转化为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，血管紧张素I到血管紧张素II的管腔内转换可以发生在皮质集合管，导致增强顶端钠的进入。
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.