Dose-dependent effects of angiotensin-(1-7) on the NHE3 exchanger and [Ca2+]i in in vivo proximal tubules
Dose-dependent effects of angiotensin-(1-7) on the NHE3 exchanger and [Ca2+]i in in vivo proximal tubules
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DOI：
10.1152/ajprenal.00401.2012
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发表时间：
2013-05-01
影响因子：
4.2
通讯作者：
de Mello-Aires, Margarida
中科院分区：
文献类型：
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作者：
Castelo-Branco, Regiane C.;Leite-Delova, Deise C. A.;de Mello-Aires, Margarida
血管紧张素-(1-7) [ANG-(1-7)] 对碳酸氢盐重吸收 (JHCO(3)(-)) 的急性直接作用通过使用 H 离子敏感微电极对大鼠体内中近端小管进行固定微灌注来评估。对照 JHCO(3)(-) 为 2.82 +/- 0.078 nmol.cm(-2).s(-1) (50)。腔内灌注小管中的ANG-(1-7) (10(-12) 或10(-9) M) 降低JHCO(3)(-) (分别为36 或60%)，但ANG-(1-7) (10(-6) M) 增加它(80%)。 A779 增加 JHCO(3)(-) (30%) 并阻止 ANG-(1-7) 对其的抑制和刺激作用。 S3226降低JHCO(3)(-) (45%)并将ANG-(1-7)的刺激作用变为抑制作用(30%)，但不影响ANG-(1-7)的抑制作用。我们的结果表明，在基础条件下，内源性 ANG-(1-7) 抑制 JHCO(3)(-)，并且 ANG-(1-7) 对 JHCO(3)(-) 的双相剂量依赖性作用是由 Mas 受体通过 Na+/H+ 交换器 3 (NHE3) 介导的。使用 fura-2 AM 监测时，细胞内 Ca2+ 浓度 ([Ca2+](i)) 的对照值为 101 +/- 2 nM (6)，ANG-(1-7)（10(-12)、10(-9) 或 10(-6)M）瞬时（3 分钟）增加该浓度（分别增加 151%、102% 或 52%）。 A779 增加 [Ca2+](i) (25%)，但削弱所有剂量的 ANG-(1-7) 对它的刺激作用。 BAPTA 或毒胡萝卜素的使用表明 ANG-(1-7) 对 [Ca2+](i) 和 JHCO(3)(-) 的剂量依赖性影响之间存在相关性。因此，ANG II 和 ANG-(1-7) 对 [Ca2+](i) 和 JHCO(3)(-) 的相反剂量依赖性作用的相互作用可能代表细胞外体积和/或 pH 变化的生理调节机制。然而，[Ca2+](i) 修饰是否是这些肽激活 NHE3 的重要直接机制，还是其他信号通路的副作用，还需要进一步研究。
The acute direct action of angiotensin-(1-7) [ANG-(1-7)] on bicarbonate reabsorption (JHCO(3)(-)) was evaluated by stationary microperfusions on in vivo middle proximal tubules in rats using H ion-sensitive microelectrodes. The control JHCO(3)(-) is 2.82 +/- 0.078 nmol.cm(-2).s(-1) (50). ANG-(1-7) (10(-12) or 10(-9) M) in luminally perfused tubules decreases JHCO(3)(-) (36 or 60%, respectively), but ANG-(1-7) (10(-6) M) increases it (80%). A779 increases JHCO(3)(-) (30%) and prevents both the inhibitory and the stimulatory effects of ANG-(1-7) on it. S3226 decreases JHCO(3)(-) (45%) and changes the stimulatory effect of ANG-(1-7) to an inhibitory effect (30%) but does not affect the inhibitory effect of ANG-(1-7). Our results indicate that in the basal condition endogenous ANG-(1-7) inhibits JHCO(3)(-) and that the biphasic dose-dependent effect of ANG-(1-7) on JHCO(3)(-) is mediated by the Mas receptors via the Na+/H+ exchanger 3 (NHE3). The control value of intracellular Ca2+ concentration ([Ca2+](i)), as monitored using fura-2 AM, is 101 +/- 2 nM (6), and ANG-(1-7) (10(-12), 10(-9), or 10(-6)M) transiently (3 min) increases it (by 151, 102, or 52%, respectively). A779 increases the [Ca2+](i) (25%) but impairs the stimulatory effect of all doses of ANG-(1-7) on it. The use of BAPTA or thapsigargin suggests a correlation between the ANG-(1-7) dose-dependent effects on [Ca2+](i) and JHCO(3)(-). Therefore, the interaction of the opposing dose-dependent effects of ANG II and ANG-(1-7) on [Ca2+](i) and JHCO(3)(-) may represent an physiological regulatory mechanism of extracellular volume and/or pH changes. However, whether [Ca2+](i) modification is an important direct mechanism for NHE3 activation by these peptides or is a side effect of other signaling pathways will require additional studies.