在存在哇巴因样因子的高血压模型中坎利酮的降压作用。

Hypotensive action of canrenone in a model of hypertension where ouabain-like factors are present.

作者信息

De Mendonca M, Grichois M L, Pernollet M G, Thorman B, Meyer P, Devynck M A, Garay R

机构信息

Inserm Unité 7, Hôpital Necker, Paris, France.

出版信息

J Hypertens Suppl. 1985 Dec;3(3):S73-5.

PMID:2856827

Abstract

It has been proposed that peripheral resistance can be increased by ouabain-like factors that are able to increase cell sodium and thereby cell calcium. Canrenone has been reported to be a partial agonist of ouabain. The effect of canrenone was investigated in rats with reduced renal mass (RRM) showing evidence of excess circulating ouabain-like factors. Wistar rats were uninephrectomized, 30% of the other kidney was removed, and they were given a 0.8% NaCl solution to drink. Half of them received 60 mg/kg per day of canrenone orally for 26 days. In RRM, the following indices of a ouabain-like activity were found: erythrocyte Na+K(+)-pump activity was decreased by 39% (P < 0.001), sodium content increased by 12% (P < 0.01), net erythrocyte sodium extrusion in plasma decreased by 20% (P < 0.01), and plasma digoxin equivalents increased by 62% (P < 0.02). Canrenone increased the IC50 for ouabain from 1.05 to 2.16 x 10(-4) mol/l (P < 0.05) in erythrocytes. In RRM with systolic blood pressure of 165 mmHg, acute administration of canrenone decreased blood pressure by 36 mmHg. Chronic administration blunted the blood pressure rise by 12, 26 and 21 mmHg at days 5, 14 and 26, respectively (P < 0.05). Haematocrit was markedly reduced in RRM (33%) and much less when treated with canrenone (37.5%). In conclusion, in contrast with spontaneously hypertensive rats, RRM hypertension is a model where a ouabain-like factor is present and in which canrenone reduces blood pressure. The hypotensive effect of canrenone may be related to a competition with ouabain-like factors.

摘要

有人提出，哇巴因样因子可增加细胞内钠含量，进而增加细胞内钙含量，从而使外周阻力增加。据报道，坎利酮是哇巴因的部分激动剂。在肾质量减少（RRM）且有证据表明循环中存在过量哇巴因样因子的大鼠中研究了坎利酮的作用。将Wistar大鼠单侧肾切除，切除另一侧肾脏的30%，并给予0.8%的NaCl溶液饮用。其中一半大鼠每天口服60mg/kg坎利酮，持续26天。在RRM大鼠中，发现了以下类似哇巴因活性的指标：红细胞钠钾泵活性降低39%（P<0.001），钠含量增加12%（P<0.01），血浆中红细胞净钠排出量降低20%（P<0.01），血浆地高辛当量增加62%（P<0.02）。坎利酮使红细胞中哇巴因的半数抑制浓度（IC50）从1.05提高到2.16×10⁻⁴mol/l（P<0.05）。在收缩压为165mmHg的RRM大鼠中，急性给予坎利酮可使血压降低36mmHg。慢性给药在第5天、第14天和第26天分别使血压升高幅度降低12mmHg、26mmHg和21mmHg（P<0.05）。RRM大鼠的血细胞比容显著降低（33%），而用坎利酮治疗时降低程度较小（37.5%）。总之，与自发性高血压大鼠不同，RRM高血压是一种存在哇巴因样因子的模型，坎利酮可降低该模型的血压。坎利酮的降压作用可能与它与哇巴因样因子的竞争有关。