Hypertensive effects of the iv administration of picomoles of ouabain

Ouabain, an endogenous digitalis compound, has been detected in nanomolar concentrations in the plasma of several mammals and is associated with the development of hypertension. In addition, plasma ouabain is increased in several hypertension models, and the acute or chronic administration of ouabain increases blood pressure in rodents. These results suggest a possible association between ouabain and the genesis or development and maintenance of arterial hypertension. One explanation for this association is that ouabain binds to the α-subunit of the Na+ pump, inhibiting its activity. Inhibition of this pump increases intracellular Na+, which reduces the activity of the sarcolemmal Na+/Ca2+ exchanger and thereby reduces Ca2+ extrusion. Consequently, intracellular Ca2+ increases and is taken up by the sarcoplasmic reticulum, which, upon activation, releases more calcium and increases the vascular smooth muscle tone. In fact, acute treatment with ouabain enhances the vascular reactivity to vasopressor agents, increases the release of norepinephrine from the perivascular adrenergic nerve endings and promotes increases in the activity of endothelial angiotensin-converting enzyme and the local synthesis of angiotensin II in the tail vascular bed. Additionally, the hypertension induced by ouabain has been associated with central mechanisms that increase sympathetic tone, subsequent to the activation of the cerebral renin-angiotensin system. Thus, the association with peripheral mechanisms and central mechanisms, mainly involving the renin-angiotensin system, may contribute to the acute effects of ouabain-induced elevation of arterial blood pressure.

Endogenous ouabain in hypertensive disorder complicating pregnancy / 华中科技大学学报（医学）（英德文版）

Expression of endogenous ouabain in placenta and the concentrations of serum ET-1 and NO were examined in 30 patients with hypertensive disorder complicating pregnancy (HDCP) and 30 healthy pregnant women to investigate the effect of endogenous ouabain on HDCP. Compared with the healthy pregnant group, the expression of endogenous ouabain dramatically increased in the HDCP groups (P<0.01). There was a significantly positive correlation between the expression of endogenous ouabain with ET-1 (r=0.5567, P<0.01), while the correlation of endogenous ouabain and NO was significantly negative (r=-0.6895, P<0.01). As expected, the correlation between ET-1 and NO was negative (r=-0.7796, P<0.01). ET-1 concentrations of maternal and cord sera in HDCP groups were significantly higher in comparison with healthy pregnant group (P<0.01). On the contrast, NO concentrations were much lower in the maternal and cord sera of HDCP groups as compared with healthy pregnant group (P<0.01). Our data suggest that endogenous ouabain is directly involved in the nosogenesis of HDCP, with accompanying decreased NO and the elevated of ET-1.

A brain soluble fraction inhibits synaptosomal membrane but not astrocyte ATPase activity

Since a brain soluble fraction (peak II) is known to be able to inhibit synaptosomal membrane Na+, K+-ATPase activity, here we attempted to compare its effect on cellular and subcellular brain components such as synaptosomal and astrocytic membranes, as well as mitochondrial preparations. Peak II highly inhibited total ATPase in synaptosomal membranes but failed to modify enzyme activity in astrocytic and mitochondrial preparations. Findings suggest cellular and subcellular specificity of peak II on brain ATPase activity.

The use of a non-linear regression approach for the analysis of the ouabain-K+ interaction with (Na++K+)-ATPase from guinea pig and rat hearts

1. The interaction between ouabain and K+ and their effects (Na+ + K+)-ATPase activity were studied using microsomes from guinea pig and rat heart. 2. Microsomes were incubated in the presence of various concentrations of K+ and ouabain and ATPase activity was estimated by measuring the inorganic phosphate liberated. The experimental data were analyzed statistically by micro-computer, using a non-linear regressión program based on the steepest descent techinique. 3. The experimental data were best fitted by a model which assumes that ouabain acts like a mixed inhibitor with respect to the apparently cooperative K+ activation of (Na+ + K+)-ATPase. This quantitative approach provieded estimates (with approximate standard deviations) of al the parameters involved in the model. 4. The inhibition constant for the uncompetitive term of the effect was 7 - to 9 - fold higher than the inhibiton constant for the competitive term for both the guinea pig and rat heart preparations. 5. The present results indicate tahta graphical analyses are helpful for illustrative purposes but sugfgests that a computerized, non-linear regression program simultaneously analyzing all the non-linearized data shoul be used to quantify the complex kinetic parameters and to discriminate objectively among possible models