Acute activation of the calcium-sensing receptor inhibits plasma renin activity in vivo
Acute activation of the calcium-sensing receptor inhibits plasma renin activity in vivo
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DOI：
10.1152/ajpregu.00238.2010
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发表时间：
2010-10-01
影响因子：
2.8
通讯作者：
Beierwaltes, William H.
中科院分区：
文献类型：
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作者：
Atchison, Douglas K.;Ortiz-Capisano, Cecilia;Beierwaltes, William H.
Atchison DK，Ortiz-Capisano MC，Beierwaltes WH.钙敏感受体的急性激活抑制体内血浆肾素活性。Am J Physiol Regul Integr Comp Physiol 299：R1020-R1026，2010.首次发表于2010年7月21日; doi：10.1152/ajpregu.00238.2010.-在体外，分泌肾素的肾小球细胞表达钙敏感受体，其激活与拟钙西那卡塞抑制肾素释放。为了测试钙敏感受体的激活是否在体内类似地抑制血浆肾素活性（PRA），我们假设钙敏感受体在体内肾小球细胞中表达，并且急性施用西那卡塞将抑制麻醉大鼠中的肾素活性。由于西那卡塞抑制甲状旁腺激素，而甲状旁腺激素可能刺激肾素活性，因此我们试图确定西那卡塞是否通过降低甲状旁腺激素来抑制肾素活性。最后，我们假设长期给予西那卡塞会抑制清醒大鼠的基础和刺激型肾素。在体内固定的大鼠皮质切片中，使用免疫荧光法将钙敏感受体和肾素定位于相同的肾小球细胞中。西那卡塞在麻醉大鼠中通过静脉推注进行急性给药，在清醒大鼠中通过经口灌胃进行慢性给药。西那卡塞急性给药使基础肾素活性从13.6 +/- 2.4降至6.1 +/- 1.1 ng ANG I.ml（-1）.h（-1）（P < 0.001）。同样，西那卡塞使呋塞米刺激的肾素从30.6 +/- 2.3降至21.3 +/- 2.3 ng ANG I.ml-1.h（-1）（P < 0.001）。在甲状旁腺切除大鼠中，西那卡塞使肾素活性从9.3 +/- 1.3降至5.2 +/- 0.5 ng ANG I.ml（-1）.h（-1）（P < 0.05），与假手术对照组相似（13.5 +/- 2.2至6.6 +/- 0.8 ng ANG I.ml（-1）.h（-1），P < 0.05）。在基础或刺激条件下，西那卡塞长期给药超过7天对PRA无显著影响。总之，钙敏感受体在体内肾小球细胞中表达，西那卡塞急性激活这些受体可抑制麻醉大鼠的PRA，不依赖于甲状旁腺激素。
Atchison DK, Ortiz-Capisano MC, Beierwaltes WH. Acute activation of the calcium-sensing receptor inhibits plasma renin activity in vivo. Am J Physiol Regul Integr Comp Physiol 299: R1020-R1026, 2010. First published July 21, 2010; doi:10.1152/ajpregu.00238.2010.-In vitro, the renin-secreting juxtaglomerular cells express the calcium-sensing receptor, and its activation with the calcimimetic cinacalcet inhibits renin release. To test whether the activation of calcium-sensing receptor similarly inhibits plasma renin activity (PRA) in vivo, we hypothesized that the calcium-sensing receptor is expressed in juxtaglomerular cells in vivo, and acutely administered cinacalcet would inhibit renin activity in anesthetized rats. Since cinacalcet inhibits parathyroid hormone, which may stimulate renin activity, we sought to determine whether cinacalcet inhibits renin activity by decreasing parathyroid hormone. Lastly, we hypothesized that chronically administered cinacalcet would inhibit basal and stimulated renin in conscious rats. Calcium-sensing receptors and renin were localized in the same juxtaglomerular cells using immunofluorescence in rat cortical slices fixed in vivo. Cinacalcet was administered acutely via intravenous bolus in anesthetized rats and chronically in conscious rats by oral gavage. Acute administration of cinacalcet decreased basal renin activity from 13.6 +/- 2.4 to 6.1 +/- 1.1 ng ANG I.ml(-1).h(-1) (P < 0.001). Likewise, cinacalcet decreased furosemide-stimulated renin from 30.6 +/- 2.3 to 21.3 +/- 2.3 ng ANG I.ml-1.h(-1) (P < 0.001). In parathyroidectomized rats, cinacalcet decreased renin activity from 9.3 +/- 1.3 to 5.2 +/- 0.5 ng ANG I.ml(-1).h(-1) (P < 0.05) similar to sham-operated controls (13.5 +/- 2.2 to 6.6 +/- 0.8 ng ANG I.ml(-1).h(-1), P < 0.05). Chronic administration of cinacalcet over 7 days had no significant effect on PRA under basal or stimulated conditions. In conclusion, calcium-sensing receptors are expressed in juxtaglomerular cells in vivo, and acute activation of these receptors with cinacalcet inhibits PRA in anesthetized rats, independent of parathyroid hormone.