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Ouabain as an amplifier of mineralocorticoid-induced hypertension
H Sekihara1, Y Yazaki, T Kojima
1Third Department of Internal Medicine, University of Tokyo Faculty of Medicine, Japan.
Abstract:
Ouabain has recently been reported to be an endogenous Na, K-ATPase inhibitor. To evaluate whether it exerts hypertensive action itself or amplifies the hypertensive action of small doses of mineralocorticoids, 5 mg deoxycorticosterone acetate (DOCA), 1 mg ouabain, or a combination of both were injected into mononephrectomized rats weekly for 6 weeks, and changes in blood pressure were evaluated. The blood pressures of control, DOCA-treated, ouabain-treated, and the combination treatment group at the sixth week were 138 +/- 3 (SE), 160 +/- 6, 144 +/- 6, and 201 +/- 14 mmHg, respectively. The blood pressure of rats given DOCA or ouabain alone was not significantly different from that of controls. In contrast, the blood pressure of rats given the combination of DOCA and ouabain was significantly higher than that of control rats and those given DOCA or ouabain separately. Cardionephromegaly and histopathological changes found in rats given the combination of DOCA and ouabain were consistent with the effects of an elevation of blood pressure. Further evaluation revealed that the amplification effect of ouabain on the hypertensive action of DOCA was dose dependent, with the minimum dose that caused the amplification effect being 0.25 mg/week. These results indicate that ouabain, although devoid of hypertensive action itself, amplifies the hypertensive action of small doses of DOCA and can cause a hypertensive state similar to that induced by larger doses of DOCA. It is inferred that the amplification effect of ouabain on mineralocorticoids is important in the genesis of hypertension.
Insights
Ouabain amplifies the blood pressure-raising effects of mineralocorticoids like deoxycorticosterone acetate (DOCA) in rats. This interaction is crucial for understanding hypertension development, even when ouabain alone does not increase blood pressure.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Renal Physiology
Background:
- Ouabain is identified as an endogenous inhibitor of Na, K-ATPase.
- Mineralocorticoids, such as deoxycorticosterone acetate (DOCA), are known to influence blood pressure regulation.
Purpose of the Study:
- To investigate whether ouabain possesses intrinsic hypertensive properties.
- To determine if ouabain amplifies the hypertensive effects of low-dose mineralocorticoids.
Main Methods:
- Mononephrectomized rats received weekly injections of DOCA, ouabain, or a combination over six weeks.
- Blood pressure, cardionephromegaly, and histopathological changes were evaluated.
Main Results:
- Neither DOCA nor ouabain alone significantly altered blood pressure compared to controls.
- Combined administration of DOCA and ouabain resulted in significantly elevated blood pressure.
- The blood pressure elevation was dose-dependent on ouabain, with amplification observed at 0.25 mg/week.
Conclusions:
- Ouabain potentiates the hypertensive action of mineralocorticoids without causing hypertension independently.
- This synergistic effect suggests a significant role for ouabain in the pathogenesis of mineralocorticoid-induced hypertension.
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