Ishikawa S, Okada K, Saito T
Department of Medicine, Jichi Medical School, Tochigi, Japan.
Endocrinology. 1992 Sep;131(3):1429-35. doi: 10.1210/endo.131.3.1505472.
The present study was undertaken to determine whether arginine vasopressin (AVP), angiotensin-II, and endothelin (ET) increase the cellular sodium concentration ([Na+]i) in cultured rat glomerular mesangial cells. [Na+]i was measured using the fluorescence indicator dye sodium-binding benzofuran isophthalate. These three vasoconstrictor hormones increased cellular free calcium ([Ca2+]i) and [Na+]i in a dose-dependent manner ([Na+]i: basal, 11.5; 10(-7) M AVP, 20.5; 10(-7) M angiotensin-II, 13.8; and 10(-7) M ET, 21.2 mM). The mobilization of [Ca2+]i was faster than that of [Na+]i. The AVP-induced increase in [Na+]i was completely blunted by the potent V1 antagonist d(CH2)5Tyr(Me)AVP. Vasoconstrictor hormones produced a biphasic cellular pH (pHi) change, characterized by a transient acidification, followed by a sustained alkalinization. The Ca(2+)-free condition markedly reduced AVP- and ET-induced increases in [Ca2+]i and [Na+]i and biphasic changes in pHi. In the Na(+)-free state, the hormonally mobilized [Ca2+]i was significantly enhanced. Basal [Na+]i decreased to below 3 mM, and there was little increase in [Na+]i after the addition of vasoconstrictor hormones, suggesting that the source of [Na+]i is extracellular space. Only early acidification was obtained in the absence of a sustained alkalinization. The [Na+]i mobilization was closely related to the biphasic change in pHi. These results indicate that AVP, ET, and angiotensin-II increase [Na+]i in glomerular mesangial cells, and that the early mobilization of [Na+]i depends on Na+/Ca2+ exchange, and the sustained phase depends on Na+/H+ exchange. The hormonally mobilized [Ca2+]i is essential for the activation of Na+/H+ exchange, and an increase in [Na+]i is suggested to play an important role in cellular alkalinization.
本研究旨在确定精氨酸加压素（AVP）、血管紧张素II和内皮素（ET）是否会增加培养的大鼠肾小球系膜细胞内的钠浓度（[Na⁺]i）。使用荧光指示剂染料钠结合苯并呋喃间苯二甲酸来测量[Na⁺]i。这三种血管收缩激素以剂量依赖性方式增加细胞内游离钙（[Ca²⁺]i）和[Na⁺]i（[Na⁺]i：基础值为11.5；10⁻⁷M AVP时为20.5；10⁻⁷M血管紧张素II时为13.8；10⁻⁷M ET时为21.2 mM）。[Ca²⁺]i的动员比[Na⁺]i更快。AVP诱导的[Na⁺]i增加被强效V1拮抗剂d(CH₂)₅Tyr(Me)AVP完全抑制。血管收缩激素引起细胞内pH（pHi）的双相变化，其特征是短暂酸化，随后是持续碱化。无钙条件显著降低了AVP和ET诱导的[Ca²⁺]i和[Na⁺]i增加以及pHi的双相变化。在无钠状态下，激素动员的[Ca²⁺]i显著增强。基础[Na⁺]i降至3 mM以下，添加血管收缩激素后[Na⁺]i几乎没有增加，这表明[Na⁺]i的来源是细胞外空间。在没有持续碱化的情况下，仅获得早期酸化。[Na⁺]i的动员与pHi的双相变化密切相关。这些结果表明，AVP、ET和血管紧张素II会增加肾小球系膜细胞内的[Na⁺]i，并且[Na⁺]i的早期动员依赖于Na⁺/Ca²⁺交换，持续阶段依赖于Na⁺/H⁺交换。激素动员的[Ca²⁺]i对于Na⁺/H⁺交换的激活至关重要，并且[Na⁺]i的增加被认为在细胞碱化中起重要作用。
