Long-term ouabain administration produces hypertension in rats.
Long-term ouabain administration produces hypertension in rats.
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长期给予哇巴因会导致大鼠出现高血压。
DOI：
10.1161/01.hyp.22.2.178
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发表时间：
1993
期刊：
影响因子：
8.3
通讯作者：
M. Pamnani
中科院分区：
文献类型：
--
作者：
C. Yuan;Paolo Manunta;J. Hamlyn;Shanwan Chen;E. Bohen;Jane Y. Yeun;Francis J. Haddy;M. Pamnani
哇巴因最近被鉴定为内源性Na（+）-K+泵抑制剂。我们长期给予哇巴因给血压正常的大鼠不同程度的减少肾质量（RRM）和正常的两肾大鼠，看看是否可以产生高血压。正常雄性Wistar大鼠和RRM为25%、60%和70%的大鼠在生理盐水中接受哇巴因（13.9 μ g/kg/天IP）4周，然后再接受哇巴因（27.8 μ g/kg/天IP）3至4周。相应对照动物仅接受溶媒。每周通过尾部体积描记法记录血压。动物接受自来水和标准大鼠饲料，70% RRM大鼠除外，其接受蒸馏水和无钠饲料。给药6至8周后，在硫代丁巴比妥麻醉下测定大鼠的直接血压。血浆，组织和尿哇巴因水平测定与特定的放射免疫分析。与对照组动物相比，接受哇巴因的动物平均血压显著升高（70% RRM，147 +/- 4 vs 116 +/- 4 mm Hg; 60% RRM，140 +/- 4 vs 107 +/- 3 mm Hg; 25% RRM，131 +/- 5 vs 100 +/- 2 mm Hg;无RRM，116 +/- 4 vs 98 +/- 5 mm Hg）。末次哇巴因给药后24小时测量的血浆哇巴因水平在接受哇巴因的动物与接受载体的动物中没有差异。然而，在接受哇巴因的动物中，肾组织哇巴因水平显著更高（6.39 +/- 1.17 vs 2.36 +/- 0.52微克/千克，P <0.05）。总之，哇巴因，长期给予，与RRM大鼠以及正常大鼠的高血压的发展。对于给定的哇巴因剂量，RRM程度较高的动物血压较高。
Ouabain has recently been identified as an endogenous Na(+)-K+ pump inhibitor. We administered ouabain chronically to normotensive rats with varying degrees of reduced renal mass (RRM) and to normal two-kidney rats to see whether hypertension could be produced. Normal male Wistar rats and rats with 25%, 60%, and 70% RRM received ouabain (13.9 micrograms/kg per day IP) in normal saline for 4 weeks followed by ouabain (27.8 micrograms/kg per day IP) for 3 to 4 more weeks. Respective control animals received vehicle only. Blood pressure was recorded weekly by tail plethysmography. Animals received tap water and standard rat chow, except for 70% RRM rats, which received distilled water and sodium-free chow. After 6 to 8 weeks of treatment, with rats under thiobutabarbital anesthesia, direct blood pressure was determined. Plasma, tissue, and urinary ouabain levels were measured with a specific radioimmunoassay. Animals receiving ouabain developed significant increases in mean blood pressure compared with control animals (70% RRM, 147 +/- 4 vs 116 +/- 4 mm Hg; 60% RRM, 140 +/- 4 vs 107 +/- 3 mm Hg; 25% RRM, 131 +/- 5 vs 100 +/- 2 mm Hg; no RRM, 116 +/- 4 vs 98 +/- 5 mm Hg). Plasma ouabain levels measured 24 hours after the last ouabain dose were not different in animals receiving ouabain vs those receiving vehicle. However, kidney tissue ouabain levels were significantly greater (6.39 +/- 1.17 vs 2.36 +/- 0.52 micrograms/kg, P < .05) in animals receiving ouabain. In conclusion, ouabain, given chronically, is associated with the development of hypertension in RRM rats as well as in normal rats. Blood pressure was greater in animals with greater degrees of RRM for a given ouabain dose.
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DOI：
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