自发性高血压大鼠传入小动脉中钠钙交换的改变。

Altered sodium-calcium exchange in afferent arterioles of the spontaneously hypertensive rat.

作者信息

Nelson L D, Mashburn N A, Bell P D

机构信息

Department of Medicine, University of Alabama at Birmingham, USA.

出版信息

Kidney Int. 1996 Dec;50(6):1889-96. doi: 10.1038/ki.1996.510.

DOI:10.1038/ki.1996.510

PMID:8943471

Abstract

Studies were performed to determine if there is a derangement in Na-Ca exchange activity in afferent (AA) and efferent (EA) arterioles from 3- and 9-week-old spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Cytosolic calcium concentration ([Ca2+]i) was assessed using microscope-based photometry in fura-2 loaded arterioles bathed in a Ringer's solution. Baseline [Ca2+]i was similar in the AA of 3- and 9-week-old WKY and SHR. In AA from 3-week-old rats, [Ca2+]i increased by 89 +/- 15 nM in WKY and by 73 +/- 13 nM in SHR during decreases in bath sodium concentration ([Na+]e) from 150 to 2 mM (Na+ replaced with n-methyl-D-glucamine). In 9-week-old hypertensive SHR (SBP = 150 mm Hg), increases in [Ca2+]i were attenuated (24 +/- 3 nM) relative to 3-week-old WKY and SHR, and 9-week-old WKY (90 +/- 9 nM; P < 0.05). Likewise, the rate of removal of Ca2+ in the continued presence of 2 mM Nae (Ca2+ sequestration and/or extrusion) was markedly reduced in AA of 9-week-old SHR (-0.15 +/- 0.03 nM/second) versus 3-week-old SHR (-0.72 +/- 0.12 nM/second) and 3- and 9-week-old WKY (-0.49 +/- 0.10 and -0.67 +/- 0.14 nM/second). In other experiments, AAs were preincubated in 1 mM ouabain to increase intracellular [Na+]. This maneuver augmented the increase in [Ca2+]i obtained with removal of Na+e; however, the responses obtained in 9-week-old SHR arterioles were still attenuated compared to those obtained in arterioles for 3- and 9-week-old WKY and 3-week-old SHR. These results suggest that exchanger number and/or sensitivity to the transmembrane Na gradient was reduced in the SHR AA. In EA, baseline [Ca2+]i was similar in 3- and 9-week-old WKY and SHR. In contrast to AA, the magnitude of Na-dependent and Na-independent changes in [Ca2+]i was not different in the EA of 3- and 9-week-old WKY and SHR. These results indicate that regulation of Na-Ca exchange activity may differ between AA and EA segments. Furthermore, diminished Na-Ca exchange and Na-independent Ca2+ sequestering/extrusion mechanisms could contribute to altered AA [Ca2+]i in the SHR.

摘要

开展了多项研究，以确定3周龄和9周龄的自发性高血压大鼠（SHR）及Wistar-Kyoto大鼠（WKY）的传入（AA）和传出（EA）小动脉中钠钙交换活性是否紊乱。使用基于显微镜的光度法，在浸浴于林格氏液中的用fura-2加载的小动脉中评估胞质钙浓度（[Ca2+]i）。3周龄和9周龄WKY和SHR的AA中的基线[Ca2+]i相似。在3周龄大鼠的AA中，当浴液钠浓度（[Na+]e）从150 mM降至2 mM（用N-甲基-D-葡糖胺替代Na+）时，WKY的[Ca2+]i增加89±15 nM，SHR增加73±13 nM。在9周龄高血压SHR（收缩压=150 mmHg）中，相对于3周龄WKY和SHR以及9周龄WKY（90±9 nM；P<0.05），[Ca2+]i的增加减弱（24±3 nM）。同样，在持续存在2 mM Nae的情况下，9周龄SHR的AA中Ca2+的清除率（Ca2+螯合和/或排出）明显低于3周龄SHR（-0.72±0.12 nM/秒）以及3周龄和9周龄WKY（-0.49±0.10和-0.67±0.14 nM/秒）（-0.15±0.03 nM/秒）。在其他实验中，将AA预先在1 mM哇巴因中孵育以增加细胞内[Na+]。这一操作增强了去除Na+e时[Ca2+]i的增加；然而，与3周龄和9周龄WKY以及3周龄SHR的小动脉相比，9周龄SHR小动脉中的反应仍然减弱。这些结果表明，SHR的AA中交换体数量和/或对跨膜Na梯度的敏感性降低。在EA中，3周龄和9周龄WKY和SHR的基线[Ca2+]i相似。与AA相反，3周龄和9周龄WKY和SHR的EA中[Ca2+]i的钠依赖性和非钠依赖性变化幅度没有差异。这些结果表明，AA和EA节段之间钠钙交换活性的调节可能不同。此外，钠钙交换减少以及非钠依赖性Ca2+螯合/排出机制可能导致SHR中AA的[Ca2+]i改变。