Kaide J, Ura N, Torii T, Nakagawa M, Takada T, Shimamoto K
Second Department of Internal Medicine, Sapporo Medical University, School of Medicine, Japan.
Am J Hypertens. 1999 Jun;12(6):611-9. doi: 10.1016/s0895-7061(99)00029-1.
The importance of increased endogenous digitalis-like factor (EDLF) in volume-expanded hypertension has been generally agreed. To further clarify the role of EDLF on the development of hypertension and renal water-sodium handling in 5/6 reduced renal mass hypertensive rats (RRM), we studied the effects of acute administration of digoxin-specific antibody Fab fragment (Digibind) in the early phase and the chronic phase of hypertension in RRM. RRM and sham-operated rats were given 1% saline for 1 or 4 weeks. RRM were injected Digibind (60 mg/kg) or vehicle (0.9% saline) intravenously in the first or fourth week under thiobutabarbital anesthesia. All sham-operated rats were administered Digibind under the same condition. Digibind altered neither blood pressure, heart rate, urine volume, nor urinary sodium excretion in sham-operated rats. However, Digibind produced a gradual but significant decline in mean arterial pressure to the level slightly above that in sham-operated rats from 153 +/- 5 to 131 +/- 5 mm Hg in the first week and from 181 +/- 6 to 129 +/- 4 mm Hg in the fourth week without any significant change in heart rate. The decrease in mean arterial pressure at 160 min after Digibind administration in the fourth week (-48 +/- 5 mm Hg) was greater than that in the first week (-22 +/- 4 mm Hg). No differences were observed in urine volume, urinary sodium excretion, or plasma norepinephrine concentration between Digibind and vehicle-treated RRM in either week. These data suggest that EDLF would contribute to both the early and chronic phase in the development of hypertension in RRM.
内源性洋地黄样因子（EDLF）增加在容量扩张性高血压中的重要性已得到普遍认可。为了进一步阐明EDLF在5/6肾切除高血压大鼠（RRM）高血压发展及肾脏水钠代谢中的作用，我们研究了在RRM高血压早期和慢性期急性给予地高辛特异性抗体Fab片段（Digibind）的影响。RRM和假手术大鼠给予1%盐水1周或4周。在硫喷妥钠麻醉下，于第1周或第4周给RRM静脉注射Digibind（60mg/kg）或溶媒（0.9%盐水）。所有假手术大鼠在相同条件下给予Digibind。Digibind对假手术大鼠的血压、心率、尿量及尿钠排泄均无影响。然而，Digibind使平均动脉压逐渐显著下降，在第1周从153±5mmHg降至略高于假手术大鼠的131±5mmHg，在第4周从181±6mmHg降至129±4mmHg，心率无显著变化。第4周给予Digibind后160分钟时平均动脉压的下降幅度（-48±5mmHg）大于第1周（-22±4mmHg）。在任何一周，Digibind组和溶媒处理的RRM组之间的尿量、尿钠排泄或血浆去甲肾上腺素浓度均无差异。这些数据表明，EDLF在RRM高血压的早期和慢性期发展中均起作用。
