Multinuclear NMR studies of intracellular cations in the prehypertensive rat kidney.
Multinuclear NMR studies of intracellular cations in the prehypertensive rat kidney.
复制标题
高血压前期大鼠肾脏细胞内阳离子的多核核磁共振研究。
DOI：
10.1016/0925-4439(94)90062-0
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Gupta,RK
中科院分区：
文献类型：
--
作者：
Dowd,TL;Gupta,RK
我们之前报道了成人自发性高血压大鼠（SHR）离体灌注肾中细胞内游离钙离子浓度的显著紊乱(J. Biol。化学267,3637-3643,1992)。为了研究细胞内游离钙或其他离子的异常是否在SHR血压升高之前发生，我们现在使用31p，19F和三重量子过滤（TQ）23Na NMR，比较了SHR和正常的年轻Wistar-Kyoto （WKY）大鼠（5 - 6周龄）灌注肾脏的细胞内游离Ca2+， Na+和pH，结果显示SHR和WKY大鼠的血压血压=120±5 mmHg和115±3 mmHg无显著差异。分别)。与成年肾脏一样，年轻高血压前期SHR和正常WKY大鼠肾脏的细胞内ATP浓度和细胞内pH值无显著差异。SHR肾脏的TQ23Na核磁共振信号高出47%，但由于生物学变异性和测量误差，这种差异无法显示出统计学意义。然而，与年龄匹配的WKY大鼠肾脏相比，年轻高血压前期SHR肾脏的O2消耗率（Na+/K+- atp酶活性的衡量指标）显著（40%，P<0.05）增加（SHR为7.25±0.75，WKY大鼠为5.17±0.18μmola O2/min g,n= 6）。此外，尽管血压没有显著差异，但与年轻正常血压的WKY大鼠相比，未发生高血压的年轻SHR大鼠肾脏细胞内游离Ca2+浓度显著（92%；P<0.02）升高（648±76 nM vs. 339±39 nM,n= 4）。因此，增加的细胞内游离Ca2+似乎是高血压前期年轻SHR肾脏的主要缺陷的一部分，它可能通过增加花生四烯酸的释放，随后通过细胞色素P450途径增加血管收缩花生四烯酸代谢物的产生，诱导成人SHR血压升高。
We previously reported a significant derangement of intracellular free calcium ion concentration in the isolated perfused kidney of adult spontaneously hypertensive rat (SHR) (J. Biol. Chem. 267, 3637–3643, 1992). In order to investigate whether an abnormality in intracellular free calcium or another ion precedes the development of elevated blood pressure in SHR, we have now compared intracellular free Ca2+, Na+and pH, using31P,19F, and triple quantum-filtered (TQ)23Na NMR, in perfused kidneys from prehypertensive young SHR and normotensive young Wistar-Kyoto (WKY) rats (5–6 weeks old) which showed no significant difference in blood pressure B.P.=120±5 mmHg and 115±3 mmHg, for SHR and WKY rats, respectively). Like the adult kidney, no significant differences in intracellular ATP concentration or intracellular pH were found between young prehypertensive SHR and normotensive WKY rat kidneys. The TQ23Na NMR signal was 47% higher in the SHR kidney, but, due to biological variability and measurement errors, this difference could not be shown to be statistically significant. However, a significant (40%;P<0.05) increase was found in O2consumption rate, a measure of the Na+/K+-ATPase activity, of the young prehypertensive SHR kidney in comparison to the age-matched WKY rat kidney (7.25±0.75 for SHR vs. 5.17±0.18μmola O2/min g for WKY rat,n= 6). Furthermore, a highly significant (92%;P<0.02) increase in intracellular free Ca2+concentration was observed in kidneys from young SHR that had noy yet been developed high blood pressure in comparison to the kidneys from young normotensive WKY rats (648±76 nM vs. 339±39 nM,n= 4, despite the fact that there was no significant difference in blood pressure. Increased intracellular free Ca2+thus appears to be part of a primary defect, in the prehypertesive young SHR kidney, which may, by way of increased release of arachidonic acid, and subsequent increased production of vasoconstricting arachidonic acid metabolites via the cytochrome P450 pathway, induce elevated blood pressure in the adult SHR.