Pharmacokinetics of Strophanthus Glycosides

The central nervous system has a key role in regulating the circulatory system by modulating the sympathetic and parasympathetic nervous systems, pituitary hormone release, and the baroreceptor reflex. Digoxin- and ouabain-like immunoreactive materials were found >20 years ago in the hypothalamic nuclei. These factors appeared to localize to the paraventricular and supraoptic nuclei and the nerve fibers at the circumventricular organs and supposed to affect electrolyte balance and blood pressure. The turnover rate of these materials increases with increasing sodium intake. As intracerebroventricular injection of ouabain increases blood pressure via sympathetic activation, an endogenous digitalis-like factor (EDLF) was thought to regulate cardiovascular system-related functions in the brain, particularly after sodium loading. Experiments conducted mainly in rats revealed that the mechanism of action of ouabain in the brain involves sodium ions, epithelial sodium channels (ENaCs) and the renin–angiotensin–aldosterone system (RAAS), all of which are affected by sodium loading. Rats fed a high-sodium diet develop elevated sodium levels in their cerebrospinal fluid, which activates ENaCs. Activated ENaCs and/or increased intracellular sodium in neurons activate the RAAS; this releases EDLF in the brain, activating the sympathetic nervous system. The RAAS promotes oxidative stress in the brain, further activating the RAAS and augmenting sympathetic outflow. Angiotensin II and aldosterone of peripheral origin act in the brain to activate this cascade, increasing sympathetic outflow and leading to hypertension. Thus, the brain Na+–ENaC–RAAS–EDLF axis activates sympathetic outflow and has a crucial role in essential and secondary hypertension. This report provides an overview of the central mechanism underlying hypertension and discusses the use of antihypertensive agents.

show abstract

“… 55 , 96 However, it is now known that ouabain is absorbed poorly (3–5%) in the intestine, indicating that it may be endogenous. 97 …”

Section: The Role Of Endogenous Digitalis In Hypertensionmentioning

confidence: 99%

The central mechanism underlying hypertension: a review of the roles of sodium ions, epithelial sodium channels, the renin–angiotensin–aldosterone system, oxidative stress and endogenous digitalis in the brain

et al. 2011

View full text Add to dashboard Cite

show abstract

“…The majority of OLI in extracts from both rat diet MF and rat adrenals was eluted with similar retention time to authentic ouabain in reverse-phase HPLC. Although the absorption rate of oral ouabain is reported to be low, being in the range of 0.7% to 7% (17), the ratios of [3H]ouabain content to OLI in each organ, ranging from 1:76 to 1:416 and being 1:278 in the adrenals, were comparable to that of the daily amount of ingested [3Hjouabain, to OLI, being 1:108. These observations raise the possibility that orally ingested ouabain, related compounds, or both, at least in part, may be accumulated mainly in the adrenal glands and act as "EDLF."…”

Section: Discussionmentioning

confidence: 88%

Exogenous Ouabain Is Accumulated in the Adrenals and Mimics the Kinetics of Endogenous Digitalis-like Factor in Rats.

et al. 1998

View full text Add to dashboard Cite

show abstract

“…Consequently, ouabain albeit at a lower level may be involved in eliminating excess sodium. It should also be considered, however, that the EOLS is known to be cleared from plasma predominantly by the kidney [41] and as a result of reduced renal function in the neonate [42] defective renal EOLS elimination and increased plasma EOLS levels might be expected.…”

Section: Discussionmentioning

confidence: 99%

Urinary Excretion of Endogenous Ouabain-Like Substance Is Reduced in NaCl Supplemented Premature Infants

et al. 1997

View full text Add to dashboard Cite

Ouabain or an isomer has been identified as endogenous ouabain-like substance (EOLS). The role of EOLS in the adaptation of premature infants to alterations of sodium balance was investigated by measuring urinary ouabain excretion serially in 9 low birth weight premature infants with (group S, mean birth weight 1,578 g, mean gestational age 30.4 weeks) and without (group NS, mean birth weight 1,537 g, mean gestational age 30.8 weeks) NaCl supplementation. The study was performed on the 7th day and weekly thereafter until the 5th week of life. NaCl supplementation was given in a dose of 3–5 and 1.5–2.5 mmol/kg/day at the postnatal ages of 8–21 and 22–35 days, respectively. Prior to NaCl supplementation, urinary ouabain excretion was similar in the two groups (146.2 ± 16.8 pg/kg/h in group S versus 180.0 ± 9.6 pg/kg/h in group NS) and remained at about the same level throughout the study when supplemental NaCl was provided. In infants of group NS, urinary ouabain excretion increased significantly by the 3rd week (p < 0.01) and no consistent change occurred later on. As a result, the differences in urinary ouabain excretion between the two groups proved to be significant during weeks 2–5 (p < 0.001). Essentially the same pattern of ouabain excretion was seen when it was expressed in terms of pg/mg creatinine. In infants receiving high sodium diet there was a significant positive correlation between urinary sodium and ouabain excretion. It is concluded that premature infants receiving low sodium intake have elevated EOLS excretion by the 3rd week of life. Although the relationship between ouabain and sodium excretion in supplemented premature infants suggests some physiological significance for sodium excretion, ouabain does not appear to be regulated by extracellular volume.

show abstract

Pharmacokinetics of Strophanthus Glycosides

Cited by 16 publications

References 48 publications

The central mechanism underlying hypertension: a review of the roles of sodium ions, epithelial sodium channels, the renin–angiotensin–aldosterone system, oxidative stress and endogenous digitalis in the brain

The central mechanism underlying hypertension: a review of the roles of sodium ions, epithelial sodium channels, the renin–angiotensin–aldosterone system, oxidative stress and endogenous digitalis in the brain

Exogenous Ouabain Is Accumulated in the Adrenals and Mimics the Kinetics of Endogenous Digitalis-like Factor in Rats.

Urinary Excretion of Endogenous Ouabain-Like Substance Is Reduced in NaCl Supplemented Premature Infants

Contact Info

Product

Resources

About