ABSTRACT
In current research reports several disease states are claimed to be associated with elevated levels of endogenous ouabain. These include hypertension, cardiac enlargement, cardiac and renal failure, and a variety of terminal disorders. It has been suggested that endogenous ouabain should be considered as a major contributor to increased blood pressure and overall cardiovascular risk. These hypotheses stand in stark contrast to decades of clinical experiences with ouabain in humans, which indicate that plant-derived ouabain is effective in treating heart failure. In patients with hypertension ouabain lowers blood pressure. These conclusive clinical experiences refute the hypothesis that ouabain in humans is a major contributor to increased blood pressure and overall cardiovascular risk. The pronounced dependence of the ouabain effects on the dose, the state of the autonomic nervous system and species-specific characteristics in pharmacokinetics may explain many of the conflicting research results that have been published on experiments with ouabain. Rodents have different sensitivities to cardiac glycosides than humans. Pharmacokinetics of cardiac glycosides in rodents are also different from humans. Therefore, caution is advised when extrapolating experimental results in rodents to humans. The mutually exclusive effects of ouabain and the endogenous inhibitor of the Na/K-ATPase observed in mammalian tissues do not support the hypothesis that this inhibitor is identical with ouabain, but favour the interpretation that De Wardener’s “third factor” is something different, which also reacts to ouabain antibodies.
ABSTRACT
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 en- dogenous 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 con- trast, NO concentrations were much lower in the maternal and cord sera of HDCP groups as com- pared 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.
ABSTRACT
Objective To compare the characteristics of endogenous ouabain(EO) secretion with the other adrenocortical hormones and determine the effects of angiotensin Ⅰ (Ang Ⅰ ), and adrenocorticotrophin(ACTH) on the secretion of EO. Methods EO was measured by radioimmunoassay from primary cultured bovine adrenocotical cells (BAC). Results ①Ouabain was determined in the media of cultured BAC. Both EO and aldosterone secretion were decreased from the outer to inner layer of the cultured adrenal cortex, and the responses to Ang Ⅰ and ACTH were higher than that in the mid layer (P ＜0. 05) and inner layer (P ＜0. 01). Cortisol secretion was activated by Ang Ⅱ or ACTH was significantly higher in the mid layer and in the inner layer than that in the outer layer. ②The time-course experiment showed that the gradually rising amounts of aldosterone and cortisol could be determined dur ing the continuous incubation to 48h with or without Ang Ⅰ or ACTH. However, EO did not increase continuously af ter 24h of incubation in the basal secreting situation and after 12h of incubation in the stimulating situation by Ang Ⅱ or ACTH. ③There were obvious drops in aldosterone and cortisol secretion from 3rd day during a 21 day-period cell culture, but the peak secretion of ouabain was in 7th day. Conclusion It suggests that the secretory mechanism might be different between EO and aldosterone or cortisol. Also, Ang Ⅱ and ACTH might be involved in the regulation of EO secretion.
ABSTRACT
Objective To explore the relationship between endogenous ouabain and the pathogenesis of hyper- tension. Methods ① Sixteen Sprague-Dawley (SD) rats were selected and randomly divided into two groups, and then the rats were injected with ouabain in dosage of 20μg/kg. d and normal saline (NS), respectively. The indirect systolic blood pressure of all the rats were recorded once a week. ②) Twenty-five lk1c (one kidney and one clipped) hypertensive rats were established and injected randomly with anti-ouabain antibody, normal rabbit IgG and normal saline, respectively. The direct blood pressure of all the lklc hypertensive rats were recorded by cannulated carotid artery for 3h after administration. Results The systolic blood pressure of rats injected with ouabain began to increase 2 weeks after ouabain administration and increased significantly at 6 weeks compared with NS group (17.7±1.2)kPa vs .(15.4±1.1)kPa, P＜ 0. 01). Anti-ouabain antibody could significantly decrease the blood pressure of 1 k1c rats, while the normal rabbit IgG could not. ConclusionThe results of this study indicate that endogenous ouabain might be one of the pathogenetic factors of hypertension.