Nakagawa H, Shimamoto K, Nakagawa M, Iimura O
Second Department of Internal Medicine, Sapporo Medical College.
Nihon Naibunpi Gakkai Zasshi. 1993 May 20;69(5):562-74. doi: 10.1507/endocrine1927.69.5_562.
The pathophysiological role of endogenous digitalis-like factor (EDLF) on blood pressure elevation was studied in reduced renal mass (RRM) rats with saline loading for a model of volume dependent hypertension. Fifty-four male Sprague-Dawley rats were operated on to remove varying proportions of their kidney mass (3/6RRM, n = 12; 4/6RRM, n = 16; 5/6RRM, n = 13) or sham operated (control, n = 13). They were given 1% NaCl to drink for 4 weeks. Urinary EDLF (UDLF) excretions were measured by radioimmunoassay using the anti-digoxin antibody, and urine volume, urinary sodium excretion and blood pressure were recorded. Systolic blood pressure was elevated significantly at the 1st week in 5/6RRM rats (from 135 +/- 3 mmHg to 157 +/- 3 mmHg) and continued to increase gradually until the 4th week (186 +/- 8 mmHg), but this was not seen in the other three groups. Urine volume and urinary sodium excretion increased after 1% saline drinking in all groups. UDLF increased significantly at the 1st day after 1% saline drinking in all groups (control: from 2.3 +/- 0.3 to 3.8 +/- 0.2, 3/6RRM: from 2.8 +/- 0.2 to 5.0 +/- 0.2, 4/6RRM: from 3.6 +/- 0.3 to 6.9 +/- 0.4, 5/6RRM: from 3.6 +/- 0.2 to 7.6 +/- 0.6 ng.digoxin/kg/day) but returned to the basal levels 2 days later in controls (3.0 +/- 0.4 ng.digoxin/kg/day) and 2 weeks later in 3/6RRM rats (3.1 +/- 0.2 ng.digoxin/kg/day) and 4/6RRM (3.3 +/- 0.3 ng.digoxin/kg/day). UDLF only remained higher than the basal level in 5/6RRM rats (2nd week: 4.7 +/- 0.4, 3rd week: 5.7 +/- 0.7, 4th week: 5.9 +/- 0.8 ng.digoxin/kg/day). A significant positive correlation was found between UDLF and systolic blood pressure (r = 0.278, p < 0.05), and between UDLF and sodium excretion (r = 0.657, p < 0.001) in 5/6RRM rats. When daily UDLF was measured in all groups during the 1st week, the integrated UDLF for 7 days of 1% saline consumption in 5/6RRM rats was significantly higher than in controls and 3/6RRM rats, and tended to be higher than in 4/6RRM rats. Integrated UDLF correlated positively with systolic blood pressure or changes in the systolic blood pressure. From these observations, it was concluded that EDLF might induce sodium excretion and that EDLF has an important role in the pathogenesis of blood pressure elevation in 5/6RRM rats.
采用生理盐水负荷的肾大部切除（RRM）大鼠作为容量依赖性高血压模型，研究内源性洋地黄样因子（EDLF）在血压升高中的病理生理作用。54只雄性Sprague-Dawley大鼠接受手术，切除不同比例的肾脏组织（3/6RRM，n = 12；4/6RRM，n = 16；5/6RRM，n = 13）或进行假手术（对照组，n = 13）。给它们饮用1%的氯化钠溶液，持续4周。使用抗地高辛抗体通过放射免疫分析法测定尿中EDLF（UDLF）的排泄量，并记录尿量、尿钠排泄量和血压。5/6RRM大鼠在第1周时收缩压显著升高（从135±3 mmHg升至157±3 mmHg），并持续逐渐升高直至第4周（186±8 mmHg），但其他三组未见此现象。所有组在饮用1%盐水后尿量和尿钠排泄量均增加。所有组在饮用1%盐水后的第1天UDLF显著增加（对照组：从2.3±0.3增至3.8±0.2，3/6RRM组：从2.8±0.2增至5.0±0.2，4/6RRM组：从3.6±0.3增至6.9±0.4，5/6RRM组：从3.6±0.2增至7.6±0.6 ng·地高辛/kg/天），但对照组在2天后（3.0±0.4 ng·地高辛/kg/天）、3/6RRM大鼠在2周后（3.1±0.2 ng·地高辛/kg/天）和4/6RRM大鼠在2周后（3.3±0.3 ng·地高辛/kg/天）恢复至基础水平。仅5/6RRM大鼠的UDLF在第2周（4.7±0.4）、第3周（5.7±0.7）和第4周（5.9±0.8 ng·地高辛/kg/天）仍高于基础水平。在5/6RRM大鼠中，UDLF与收缩压之间存在显著正相关（r = 0.278，p < 0.05），UDLF与钠排泄之间也存在显著正相关（r = 0.657，p < 0.001）。在第1周对所有组进行每日UDLF测量时，5/6RRM大鼠饮用1%盐水7天的UDLF积分显著高于对照组和3/6RRM大鼠，且有高于4/6RRM大鼠的趋势。UDLF积分与收缩压或收缩压变化呈正相关。从这些观察结果得出结论，EDLF可能诱导钠排泄，并且EDLF在5/6RRM大鼠血压升高的发病机制中起重要作用。
