SPONTANEOUSLY HYPERTENSIVE RAT VASCULAR SMOOTH-MUSCLE CELLS IN CULTURE EXHIBIT INCREASED GROWTH AND NA+/H+ EXCHANGE
SPONTANEOUSLY HYPERTENSIVE RAT VASCULAR SMOOTH-MUSCLE CELLS IN CULTURE EXHIBIT INCREASED GROWTH AND NA+/H+ EXCHANGE
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DOI：
10.1172/jci113964
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发表时间：
1989-03-01
影响因子：
15.9
通讯作者：
ALEXANDER, RW
中科院分区：
文献类型：
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作者：
BERK, BC;VALLEGA, G;ALEXANDER, RW
导致自发性高血压大鼠（SHR）血管平滑肌细胞（VSMC）生长和血管反应性异常的细胞机制尚未明确。由于Na+/H+交换，我们以前在培养的VSMC中已经证明，在介导生长因子反应中起着至关重要的作用，我们假设SHR生长调节的异常可能反映在这种转运蛋白的活性中。为了验证这一假设，我们研究了12周龄SHR和Wistar京都（WKY）动物主动脉VSMC早期传代培养（< 6）中的DNA合成和Na+/H+交换（以阿米洛利敏感的细胞内碱化或Na+内流速率测量）。去血清的SHR VSMC对10%血清的反应更快，[3 H]胸苷掺入增加439%，而WKY对照组为191%。通过荧光pH测量确定的基础细胞内pH（pHi）值为7.37 ±。0.04和7.27 .+-。0.03在早代SHR和WKY组中，差异有统计学意义（P < 0.05）。SHR VSMC的酸恢复（初始pHi = 6.8）比WKY VSMC快，如通过碱化（1.8 ± 1.5）测量的。0.6相对于0.8 ±。0.2 mmol H+/升min，P < 0.05）或阿米洛利敏感的22 Na+内流（14.5 ± 0.05）。1.2 vs. 4.0 .+-。0.5 nmol Na+/mg蛋白min，P < 0.05）。与WKY细胞相比，早期传代SHR VSMC表现出2.5倍的碱化和阿米洛利敏感的22 Na+内流，以响应100 nM血管紧张素II。在连续传代过程中，WKY细胞获得了增强的Na/H+交换和生长速率，因此到第6代，这些差异不再存在。从体内神经体液环境中取出的SHR VSMC的早期培养物中的这些发现表明，SHR中Na+/H+交换的增加可能重新选择Na+稳态的改变，这可能有助于改变SHR VSMC功能，例如增强生长和血管反应性。
The cellular mechanism responsible for abnormalities in spontaneously hypertensive rat (SHR) vascular smooth muscle cells (VSMC) growth and vasoreactivity are not defined. Because Na+/H+ exchange, which we have previously demonstrated in cultured VSMC, plays an essential role in mediating growth factor responses, we hypothesized that abnormalities in SHR growth regulation might be reflected in the activity of this transporter. To test this hypothesis, we studied DNA synthesis and Na+/H+ exchange (measured as the rate of amiloride-sensitive intracellular alkalinization or Na+ influx) in early subcultures (< 6) of aortic VSMC from 12-wk-old SHR and Wistar Kyoto (WKY) animals. Serum-deprived SHR VSMC grew more rapidly in response to 10% serum with an increase in [3H]thymidine incorporation of 439% compared with 191% in WKY controls. Basal intracellular pH (pHi) values determined by fluorescent pH measurements were 7.37 .+-. 0.04 and 7.27 .+-. 0.03 (P < 0.05) in early passage SHR and WKY, respectively. Acid recovery (inital pHi = 6.8) by SHR VSMC was faster than by WKY VSMC as measured by alkalinization (1.8 .+-. 0.6 vs. 0.8 .+-. 0.2 mmol H+/liter .cntdot. min, P < 0.05) or by amiloride-sensitive 22Na+ influx (14.5 .+-. 1.2 vs. 4.0 .+-. 0.5 nmol Na+/mg protein .cntdot. min, P < 0.05). In comparison to WKY cells early passage SHR VSMC exhibited 2.5-fold greater alkalinization and amiloride-sensitive 22Na+ influx in response to 100 nM angiotensin II. During serial passage, WKY cells acquired enhanced Na/H+ exchange and growth rates so that by passage 6, these differences were no longer present. These findings in early cultures of SHR VSMC, removed from the in vivo neurohumoral milieu, suggest that increased Na+/H+ exchange in SHR may refelect alterations in Na+ homeostasis that might contribute to altered SHR VSMC function such as enhanced growth and vasoreactivity.