Inhibition of calcium signaling in descending vasa recta endothelia by ANG II.
Inhibition of calcium signaling in descending vasa recta endothelia by ANG II.
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DOI：
10.1152/ajpheart.2000.278.4.h1248
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发表时间：
2000-04
期刊：
影响因子：
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通讯作者：
T. Pallone;E. Silldorff;Z. Zhang
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作者：
T. Pallone;E. Silldorff;Z. Zhang
在加载 fura 2 的血管中检查了外髓直降血管 (OMDVR) 内皮细胞对 ANG II 的细胞内钙 ([Ca(2+)](i)) 反应。 Abluminal ANG II (10(-8) M) 导致 [Ca(2+)](i) 与内皮细胞的静息 [Ca(2+)](i) (r = 0. 82) 成比例下降。 ANG II (10(-8) M) 还抑制缓激肽 (BK, 10(-7) M) 产生的 [Ca(2+)](i) 反应的两个阶段，835 +/- 201 对比 159 +/- 30 nM（峰值期）和 169 +/- 26 对比 103 +/- 14 nM（平台期）（平均值 +/- SE）。 Luminal ANG II 将 BK (10(-7) M) 刺激的平台 [Ca(2+)](i) 从 180 +/- 40 降低至 134 +/- 22 nM，而不引起血管收缩。在应用 Luminal 后，将 Abluminal ANG II 添加到浴中，进一步将 [Ca(2+)](i) 降低至 113 +/- 9 nM 并收缩血管。毒胡萝卜素 (TG) 预处理后，ANG II (10(-8) M) 导致 [Ca(2+)](i) 从 352 +/- 149 降至 105 +/- 37 nM。这种效应发生在 ANG II 阈值浓度为 10(-10) M 时，在 10(-8) M 时达到最大。ANG II 抑制 Ca(2+) 进入[Ca(2+)](i) 耗尽的内皮细胞的速率和 Mn(2+) 进入[Ca(2+)](i) 充满的内皮细胞的速率。相反，ANG II 升高髓质升肢厚层和外髓集合管中的 [Ca(2+)](i)，使 [Ca(2+)](i) 从基线 99 +/- 33 和 53 +/- 11 分别增加到峰值 200 +/- 47 和 65 +/- 11 nM。我们得出结论，OMDVR内皮细胞不太可能是髓质中ANG II刺激的NO产生的来源，但束间肾单位可能释放Ca(2+)依赖性血管舒张剂来调节血管束中的血管舒缩张力。
The intracellular calcium ([Ca(2+)](i)) response of outer medullary descending vasa recta (OMDVR) endothelia to ANG II was examined in fura 2-loaded vessels. Abluminal ANG II (10(-8) M) caused [Ca(2+)](i) to fall in proportion to the resting [Ca(2+)](i) (r = 0. 82) of the endothelium. ANG II (10(-8) M) also inhibited both phases of the [Ca(2+)](i) response generated by bradykinin (BK, 10(-7) M), 835 +/- 201 versus 159 +/- 30 nM (peak phase) and 169 +/- 26 versus 103 +/- 14 nM (plateau phase) (means +/- SE). Luminal ANG II reduced BK (10(-7) M)-stimulated plateau [Ca(2+)](i) from 180 +/- 40 to 134 +/- 22 nM without causing vasoconstriction. Abluminal ANG II added to the bath after luminal application further reduced [Ca(2+)](i) to 113 +/- 9 nM and constricted the vessels. After thapsigargin (TG) pretreatment, ANG II (10(-8) M) caused [Ca(2+)](i) to fall from 352 +/- 149 to 105 +/- 37 nM. This effect occurred at a threshold ANG II concentration of 10(-10) M and was maximal at 10(-8) M. ANG II inhibited both the rate of Ca(2+) entry into [Ca(2+)](i)-depleted endothelia and the rate of Mn(2+) entry into [Ca(2+)](i)-replete endothelia. In contrast, ANG II raised [Ca(2+)](i) in the medullary thick ascending limb and outer medullary collecting duct, increasing [Ca(2+)](i) from baselines of 99 +/- 33 and 53 +/- 11 to peaks of 200 +/- 47 and 65 +/- 11 nM, respectively. We conclude that OMDVR endothelia are unlikely to be the source of ANG II-stimulated NO production in the medulla but that interbundle nephrons might release Ca(2+)-dependent vasodilators to modulate vasomotor tone in vascular bundles.