14β‐Hydroxyprogesterone binds to the digitalis receptor, inhibits the sodium pump and enhances cardiac contractility

Böse, Dirk; Elliott, D.; Kobayashi, Takakazu; Templeton, J. F.; Kumar, Vinay; LaBella, Frank S.

doi:10.1111/j.1476-5381.1988.tb11453.x

Cited by 33 publications

(7 citation statements)

References 23 publications

(29 reference statements)

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“…Little information is available with regard to the effect of progesterone on cardiac contractility. In few studies, progesterone derivatives have been shown to enhance contractility of isolated cardiac muscle (57,58). In addition to the dependence of cardiovascular autonomic control on the type of gonadal hormones (estrogen vs. progesterone), the cyclic variation in hormonal levels is also an important modulator of the autonomic drive.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal assessment of the effects of oestrogen on blood pressure and cardiovascular autonomic activity in female rats

El‐Mas

Abdel‐Rahman

2009

Clin Exp Pharma Physio

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1. Published data concerning the effect of ovarian hormones on hemodynamic variability is contradictory. This study employed, for the first time, radiotelemetric hemodynamic monitoring to investigate the long-term effects of chronic estrogen depletion and repletion on cardiovascular autonomic control and arterial baroreflex sensitivity (BRS) in female rats. 2. Blood pressure (BP), heart rate (HR), and +dP/dtmax of arterial pressure (an estimate of myocardial contractility) were monitored in sham-operated (SO), ovariectomized (OVX), and estrogen-replaced OVX rats (OVXE2) for 16 weeks. Cardiovascular autonomic control and baroreflexes were assessed by frequency domain analysis of interbeat intervals (IBI) and systolic BP (SBP). 3. Compared with SO rats, OVX rats exhibited (i) no changes in BP, (ii) short-lived decreases in HR, and (iii) sustained reductions in dP/dtmax of arterial pressure. The high frequency (HF, 0.75-3 Hz) and low frequency (LF, 0.25-0.75 Hz) components of spectral power of IBI were significantly decreased and increased, respectively, by ovariectomy. An increase in the IBILF/HF ratio in OVX rats suggested a shift in the cardiac sympathovagal balance towards sympathetic dominance. Index α, the spectral index of spontaneous BRS, was reduced by OVX. 4. Estrogen replacement caused significant reductions in BP and HR and reversed OVX-induced changes in +dP/dtmax of arterial pressure and cardiac autonomic activity. The LF oscillations of SBP were reduced in OVX-E2 treated rats, suggesting a reduction in vascular sympathetic tone by estrogen. 5. These findings highlight the importance of long-term estrogen therapy in rectifying the detrimental cardiovascular and baroreflex influences caused by depletion of ovarian hormones.

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Section: Discussionmentioning

confidence: 99%

Longitudinal assessment of the effects of oestrogen on blood pressure and cardiovascular autonomic activity in female rats

El‐Mas

Abdel‐Rahman

2009

Clin Exp Pharma Physio

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“…This is further complicated by the significant heterogeneity in methods of defining SS. [5][6][7][8]20 Increased intracellular sodium ([Na ϩ ] i ,) assessed primarily in circulating blood cells, is one of the most consistently reported abnormalities of cation metabolism in essential hypertension, although a link between intracellular cation metabolism and salt-induced elevation of BP has not been established. A number of epidemiologic studies have documented a direct correlation between [Na ϩ ] i and BP in AA but not in non-AA.…”

mentioning

confidence: 99%

Determinants of Salt Sensitivity in Black and White Normotensive and Hypertensive Women

Wright

Rahman²,

Scarpa

et al. 2003

Hypertension

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Abstract-Salt sensitivity (SS) has been linked to human hypertension. We examined ethnic differences in the relation between SS; erythrocyte sodium (Na ; and sodium pump activity in African-American (AA) and white women. In a crossover protocol, similar numbers of normotensive, hypertensive, AA, and white women were randomized to 7 days of a 20 meq/d and a Ͼ200 meq/d salt diet (nϭ199). After an overnight inpatient stay, group differences in supine blood pressure (BP), heart rate, erythrocyte cations, and sodium pump activity were measured. The prevalence of SS (53.5% vs 51%) and salt resistance (26.3% vs 30.0%) was similar in both races. Greater mean BP increase with salt loading was seen in AA vs white hypertensives but not between the normotensive women. In hypertensives, increase in mean arterial pressure was 12.6 vs 8.2 mm Hg in AAs vs whites, respectively (PϽ0.01), and for systolic BP, it was 23 vs 14.8 mm Hg (PϽ0.01). Higher Na i were positively correlated with salt responsiveness in AA but not in white women. Sodium pump activity was similar between groups, although the change in maximal activity trended to vary inversely with SS in AA. In closely matched AA and white women, the prevalence of SS is similarly high in both races, although the magnitude of BP increase is greater in AA hypertensives. In AA but not in whites, SS is positively associated with Na ssential hypertension continues to be a major cause of morbidity and mortality in industrialized populations of the world and one for which there is no known cause. In the United States, the prevalence of hypertension increases with age, and at about age 55, the prevalence becomes greater in women versus men. 1 More than half of white and three fourths of African-American (AA) women will develop hypertension by age 65 to 74 years. Acute blood pressure (BP) elevation with increasing salt intake (salt sensitivity [SS]) is commonly reported in large segments of the population, especially in those with renal disease, diabetes, obesity, hypertension, and older age and in AA. 2,3 BP sensitivity to salt might also predict chronic BP elevation, and normotensives with this trait are more likely to develop hypertension. 2,4 However, the pathophysiology of SS and its progression to hypertension remain poorly understood. This is further complicated by the significant heterogeneity in methods of defining SS. [5][6][7][8]20 Increased intracellular sodium ([Na ϩ ] i ,) assessed primarily in circulating blood cells, is one of the most consistently reported abnormalities of cation metabolism in essential hypertension, although a link between intracellular cation metabolism and salt-induced elevation of BP has not been established. A number of epidemiologic studies have documented a direct correlation between [Na ϩ ] i and BP in AA but not in non-AA. 9 -15 Racial differences in several membrane sodium-transport systems have also been reported. 14 -16 Na,KATPase (sodium pump) is a principal regulator of [Na ϩ ] i . Lower sodium pump activity has been reported in AA versus...

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“…However, in plasma from other pregnant women and from healthy subjects, the amounts of digoxin-like substances are clearly lower than in the urine, but the chromatographic profile is essentially similar (Vinge, unpublished results). The wide range of fractions containing digoxin-like activity is consistent with the presence of several digoxin-like substances and it cannot be ruled out that they derive from a common molecular structure, possibly progesterone (Bose et al 1988).…”

Section: Concentration ( M )mentioning

confidence: 93%

Progesterone, some Progesterone Derivatives and Urinary Digoxin‐Like Substances from Pregnant Women in Radioimmuno‐ and ⁸⁶Rb‐Uptake Assays of Digoxin

Vinge

Helgesen-Rosendal

Bäckström

1988

Pharmacology & Toxicology

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Progesterone and some derivatives were tested in a radioimmunoassay (RIA) of digoxin and in a bioassay measuring the 86Rb-uptake into red blood cells as an index of Na+, K+-ATPase activity. The digitalis-like activity of the hormones was compared with that found in chromatographic fractions of material extracted from the urines of pregnant women at term. Progesterone at concentrations greater than 10(-6) M cross-reacted in the RIA, and at 10(-3) M it decreased 86Rb-uptake by 18%. The anaesthetic progesterone derivates 5 alpha-pregnane-3 alpha-ol-20-one and 5 alpha-pregnane-3,20-dione crossreacted to a lesser degree in the RIA and lacked effect in the bioassay. Similar results were obtained with pregnandiol-glucuronide, the major urinary metabolite of progesterone. In contrast, several fractions of the urinary material had significant effects in both assays. It is concluded that the digitalis-like activity of progesterone is not coupled to properties associated with its anaesthetic effects. Furthermore, although progesterone may account for a part of the endogenous digoxin-like substances in serum of neonates and pregnant women, neither progesterone proper nor pregnandiol-glucuronide explains the great amount of digoxin-like substances found in the urines.

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14β‐Hydroxyprogesterone binds to the digitalis receptor, inhibits the sodium pump and enhances cardiac contractility

Cited by 33 publications

References 23 publications

Longitudinal assessment of the effects of oestrogen on blood pressure and cardiovascular autonomic activity in female rats

Longitudinal assessment of the effects of oestrogen on blood pressure and cardiovascular autonomic activity in female rats

Determinants of Salt Sensitivity in Black and White Normotensive and Hypertensive Women

Progesterone, some Progesterone Derivatives and Urinary Digoxin‐Like Substances from Pregnant Women in Radioimmuno‐ and ⁸⁶Rb‐Uptake Assays of Digoxin

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14β‐Hydroxyprogesterone binds to the digitalis receptor, inhibits the sodium pump and enhances cardiac contractility

Cited by 33 publications

References 23 publications

Longitudinal assessment of the effects of oestrogen on blood pressure and cardiovascular autonomic activity in female rats

Longitudinal assessment of the effects of oestrogen on blood pressure and cardiovascular autonomic activity in female rats

Determinants of Salt Sensitivity in Black and White Normotensive and Hypertensive Women

Progesterone, some Progesterone Derivatives and Urinary Digoxin‐Like Substances from Pregnant Women in Radioimmuno‐ and 86Rb‐Uptake Assays of Digoxin

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Progesterone, some Progesterone Derivatives and Urinary Digoxin‐Like Substances from Pregnant Women in Radioimmuno‐ and ⁸⁶Rb‐Uptake Assays of Digoxin