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Journal articles on the topic 'Endogenous digitalis-like factor (EDLF)'

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Published: 4 June 2021

Last updated: 4 February 2022

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1

Clerico, A., A. Paci, M. G. Del Chicca, P. Biver, and O. Giampietro. "Endogenous Digitalis-Like Factors in Human Milk." Clinical Chemistry 38, no. 4 (April 1, 1992): 504–6. http://dx.doi.org/10.1093/clinchem/38.4.504.

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Abstract We measured the concentration of endogenous digitalis-like factors (EDLFs) in milk or colostrum of women during nursing on different days after delivery. EDLF concentrations were assayed by a solid-phase RIA involving antidigoxin antibodies and by a radioreceptor assay (RRA) involving human placenta Na+/K(+)-ATPase. The mean (SD) EDLF concentrations as measured by RIA were 35.6 (19.4) ng of digoxin equivalents per liter in milk samples (n = 37) and 61.3 (12.5) ng/L in colostrum samples (n = 5); the mean EDLF concentration as measured by RRA in milk samples (n = 11) was 573 (717) ng/L (range 0-2098). EDLF concentration in milk is greater than circulating concentrations in healthy adults but is comparable with serum concentration in the third trimester of pregnancy. In milk and serum samples (n = 8) collected at the same time, heating and (or) extracting with Sep-Pak C18 cartridges before the RIA produced significantly different EDLF values from those in untreated serum (P less than 0.001) and milk (P = 0.035). EDLF in milk appeared to be not bound or weakly bound to milk protein, as indicated by the fact that boiling did not increase the digoxin-like immunoreactivity.

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2

Paci, A., G. Ciarimboli, and P. Biver. "Human placenta radioreceptor assay with digoxin and ouabain to detect endogenous digitalis-like factor(s) in human plasma and urine." Clinical Chemistry 42, no. 2 (February 1, 1996): 270–78. http://dx.doi.org/10.1093/clinchem/42.2.270.

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Abstract We describe the optimization and validation of a clinically feasible radioreceptor assay to detect endogenous digitalis-like factor(s) (EDLF) in human plasma and urine. The assay is based on the competitive replacement of 125I-labeled digoxin on human placenta membranes by ligands present in sample extracts. Digoxin and ouabain were used as calibrators. We also describe simple and effective methods for extraction and enrichment of EDLF from human plasma and urine. Assay sensitivity and precision were enhanced by using a sequential saturation technique with appropriate concentrations of tracer and receptors. Filtration was used to separate bound from free ligand. A two-step solid-state extraction with acetonitrile allowed the separation of two EDLFs with different polarity (EDLF-1 and EDLF-2) from the same plasma sample. A one-step solid-state extraction with methanol was suitable for urine. EDLF-1 and EDLF-2 in healthy adults were respectively 204 +/- 155 and 207 +/- 423 pmol/L ouabain equivalents, or 312 +/- 241 and 302 +/- 581 pmol/L digoxin equivalents. Plasma concentrations of EDLFs in newborns and pregnant women were higher than in healthy adults, and the concentrations in urine were higher than in plasma. Several cross-reactivity experiments showed that physiological concentrations of endogenous steroids and lipids did not inhibit binding, and supported the hypothesis that EDLFs are endogenous compounds other than the steroids and lipids also investigated.

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3

Hamlyn, J. M. "Increased levels of a humoral digitalis-like factor in deoxycorticosterone acetate-induced hypertension in the pig." Journal of Endocrinology 122, no. 1 (July 1989): 409–20. http://dx.doi.org/10.1677/joe.0.1220409.

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ABSTRACT Plasma levels of an endogenous digitalis-like factor (EDLF) and atrial peptides were followed in pigs confined to metabolic cages during the development of deoxycorticosterone acetate (DOCA)-induced hypertension. During the first 2 days of DOCA treatment, urinary sodium excretion decreased and the plasma levels of renin and atrial peptide fell significantly. During this period, plasma levels of EDLF increased > 30-fold from a baseline of <0·25 to 9·72 nmol ouabain equivalents/l. Between days 2 and 5 of DOCA treatment, urinary sodium returned to preDOCA levels ('mineralocorticoid escape') and during this period significant increases of atrial peptide and mean arterial pressure (MAP) and a decrease in EDLF were found. Following mineralocorticoid escape there was a secondary rise in levels of EDLF and atrial peptide and both phenomena correlated with MAP (EDLF, r = 0·87, P< 0·05; atrial peptide, r = 0·9, P< 0·05) and with each other (r = 0·96, P < 0·05) over a 20-day period. Acute expansion of extracellular fluid volume before DOCA elicited significant increments in plasma EDLF and atrial peptide. Volume loading during chronic DOCA treatment increased plasma EDLF significantly whereas no response of atrial peptide was detected. These results suggest that DOCA affects the reactivity of mechanisms involved in the perception of and/or response to acute changes in volume status. However, neither EDLF nor atrial peptide appear to be viable candidates as direct mediators of mineralocorticoid escape. Finally, the nature of the changes found in EDLF and atrial peptide levels during DOCA treatment suggest that these factors are involved in the long-term control of blood pressure in this model of low renin hypertension. Journal of Endocrinology (1989) 122, 409–420

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4

Buckalew, Vardaman M. "Role of endogenous digitalis-like factors in the clinical manifestations of severe preeclampsia: a systematic review." Clinical Science 132, no. 12 (June 21, 2018): 1215–42. http://dx.doi.org/10.1042/cs20171499.

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Endogenous digitalis-like factor(s), originally proposed as a vasoconstrictor natriuretic hormone, was discovered in fetal and neonatal blood accidentally because it cross-reacts with antidigoxin antibodies (ADAs). Early studies using immunoassays with ADA identified the digoxin-like immuno-reactive factor(s) (EDLF) in maternal blood as well, and suggested it originated in the feto–placental unit. Mammalian digoxin-like factors have recently been identified as at least two classes of steroid compounds, plant derived ouabain (O), and several toad derived bufodienolides, most prominent being marinobufagenin (MBG). A synthetic pathway for MBG has been identified in mammalian placental tissue. Elevated maternal and fetal EDLF, O and MBG have been demonstrated in preeclampsia (PE), and inhibition of red cell membrane sodium, potassium ATPase (Na, K ATPase (NKA)) by EDLF is reversed by ADA fragments (ADA-FAB). Accordingly, maternal administration of a commercial ADA-antibody fragment (FAB) was tested in several anecdotal cases of PE, and two, small randomized, prospective, double-blind clinical trials. In the first randomized trial, ADA-FAB was administered post-partum, in the second antepartum. In the post-partum trial, ADA-FAB reduced use of antihypertensive drugs. In the second trial, there was no effect of ADA-FAB on blood pressure, but the fall in maternal creatinine clearance (CrCl) was prevented. In a secondary analysis using the pre-treatment maternal level of circulating Na, K ATPase (NKA) inhibitory activity (NKAI), ADA-FAB reduced the incidence of pulmonary edema and, unexpectedly, that of severe neonatal intraventricular hemorrhage (IVH). The fall in CrCl in patients given placebo was proportional to the circulating level of NKAI. The implications of these findings on the pathophysiology of the clinical manifestations PE are discussed, and a new model of the respective roles of placenta derived anti-angiogenic (AAG) factors (AAGFs) and EDLF is proposed.

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5

Bagrov, Alexey Ya. "Endogenous Digoxin-Like Factor: Possible Emergency Implications." Prehospital and Disaster Medicine 7, no. 1 (March 1992): 65–68. http://dx.doi.org/10.1017/s1049023x00039236.

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SummaryThe existence of endogenously produced, digoxin-like factor(s) is clear. The implications of die presence of this circulating substance are substantial for the practice of emergency medical care. Clearly, EDLF plays an important role in the generation of dysrhythmias associated with an AMI. Treatment with AA could become routine early in the course of management of some patients with AMI and in die treatment of some forms of hypertension

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6

NAKAGAWA, Hidehisa, Kazuaki SHIMAMOTO, Motoya NAKAGAWA, and Osamu IIMURA. "The Role of Endogenous Digitalis-Like Factor on Hypertensive Mechanisms in Reduced Renal Mass Hypertensive Rats." Folia Endocrinologica Japonica 69, no. 5 (1993): 562–74. http://dx.doi.org/10.1507/endocrine1927.69.5_562.

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7

Sophocleous, A., I. Elmatzoglou, and A. Souvatzoglou. "Circulating endogenous digitalis-like factor(s) (EDLF) in man is derived from the adrenals and its secretion is ACTH-dependent." Journal of Endocrinological Investigation 26, no. 7 (July 2003): 668–74. http://dx.doi.org/10.1007/bf03347027.

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8

Yamada, K., A. Goto, C. Hui, N. Yagi, H. Nagoshi, M. Sasabe, and T. Sugimoto. "Role of ouabainlike compound in rats with reduced renal mass-saline hypertension." American Journal of Physiology-Heart and Circulatory Physiology 266, no. 4 (April 1, 1994): H1357—H1362. http://dx.doi.org/10.1152/ajpheart.1994.266.4.h1357.

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Ouabainlike compound (OLC) has recently been identified as a likely mammalian endogenous digitalis-like factor (EDLF) from human plasma. In this study, plasma levels of OLC were determined to assess the role of OLC in a model known as volume-expanded, reduced renal mass (RRM)-saline (S) hypertension in rats with use of a newly developed radioimmunoassay for ouabain. In the first experiment, at 3 wk after subtotal nephrectomy and drinking 1% saline solution, sysolic blood pressure (SBP) of 18 rats with reduced renal mass (RRM-S rats) was significantly higher than in 17 sham-operated saline-drinking control (C-S) rats [154 +/- 4 (SE) vs. 132 +/- 2 mmHg; P < 0.01]. Plasma OLC levels were 355 +/- 68 pmol/l in RRM-S rats, sevenfold higher than in C-S rats (54 +/- 4 pmol/l; P < 0.01). In the second experiment, we measured plasma OLC levels of 10 RRM-S, 12 sham-operated control (C), and 10 subtotally nephrectomized rats drinking distilled water (RRM rats). Concomitant with a marked increase in blood pressure (203 +/- 5 mmHg), RRM-S rats showed significantly higher plasma OLC levels compared with C and RRM rats (RRM-S 114 +/- 24, C 47 +/- 11, and RRM 52 +/- 9 pmol/l; P < 0.05). In both experiments, plasma OLC levels correlated significantly with SBP (P < 0.05). These findings suggest that plasma OLC shows a similar behavior to that of EDLFs or Na(+)-K(+)-adenosinetriphosphatase inhibitors reported in previous publications and may play a role in hypertensive mechanisms in rats with RRM and excess Na intake.

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9

K�lbel, Franti?ek, and Vratislav Schreiber. "The endogenous digitalis-like factor." Molecular and Cellular Biochemistry 160-161, no. 1 (1996): 111–15. http://dx.doi.org/10.1007/bf00240039.

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10

Vinge, Ellen, Eva Marie T. Erfurth, and Stefan Lundin. "Effects of adrenal function tests on the levels of endogenous digitalis-like substances and some pituitary hormones." Acta Endocrinologica 128, no. 1 (January 1993): 29–34. http://dx.doi.org/10.1530/acta.0.1280029.

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In order to study the influence of the hypothalamic-pituitary-adrenal axis on the levels of endogenous digitalis-like substances (EDLS) in plasma and urine, eight healthy subjects (25–40 years old) were given dexamethasone 1 mg orally and tetracosactide (an ACTH analog) 0.25 mg iv, on separate occasions. The circulating levels of EDLS, TSH, PRL and AVP following administration of either test drug, and under control conditions, were measured by a RIA for digoxin and specific RIAs for each hormone. Plasma cortisol was measured by liquid chromatography. The area under the curve (AUC) of hormone levels between 08.00 and 09.30 was used for data comparisons. Urine was collected before and after each test dose, and analysed for cortisol levels by gas chromatography/mass spectrometry, and for digitalis-like activity both by RIA and by a bioassay measuring 86Rb-uptake into red blood cells. Dexamethasone suppressed the AUC of plasma and urine levels of cortisol (p=0.0001 and p<0.01, respectively) and immunoreactive EDLS (p=0.0007 and p<0.01), as well as serum levels of TSH (p=0.0002) and PRL (p=0.001), but did not alter AVP levels. The biological digitalis-like activity in the urine measured by the 86Rb-uptake assay was decreased, but not to a statistically significant degree. ACTH increased the levels of cortisol in plasma (p=0.0001) and urine (p<0.01) and the immunoreactive EDLS in plasma (p = 0.03), but not in urine. There were no effects of ACTH on TSH, PRL or AVP. There are alternative explanations for the discrepancy between the effects on EDLS levels in plasma and urine: methodological difficulties in quantitating EDLS, the doses of dexamethasone and ACTH used for the adrenal function tests, and that other hypothalamic or pituitary factors than ACTH may contribute to a significant degree in the regulation of EDLS levels. Taken together, the results of the present study support the hypothesis that EDLS is of adrenal origin, rather than hypothalamic or pituitary.

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11

Haddy, Francis J. "Endogenous Digitalis-like Factor or Factors." New England Journal of Medicine 316, no. 10 (March 5, 1987): 621–23. http://dx.doi.org/10.1056/nejm198703053161010.

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12

Goto, Atsuo, Kaoru Yamada, Noriko Yagi, Chen Hui, Yoshitake Terano, and Tsuneaki Sugimoto. "Ouabain as Endogenous Digitalis-Like Factor In Animals?" Clinical Chemistry 38, no. 1 (January 1, 1992): 161–62. http://dx.doi.org/10.1093/clinchem/38.1.161a.

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13

Goto, A., K. Yamada, M. Ishii, and T. Sugimoto. "How best to detect endogenous digitalis-like factor?" Clinical Chemistry 34, no. 11 (November 1, 1988): 2392–93. http://dx.doi.org/10.1093/clinchem/34.11.2392.

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14

BALZAN, S., S. GHIONE, A. CLERICO, and U. MONTALI. "Endogenous Digitalis-like Factor(s) in Human Plasma:." Annals of the New York Academy of Sciences 488, no. 1 Membrane Path (December 1986): 570–72. http://dx.doi.org/10.1111/j.1749-6632.1986.tb46605.x.

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15

Paci, Anna, Silvana Balzan, Adreina Ledda, and Sergio Ghoine. "Different methods for measuring endogenous digitalis-like factor(s)." Journal of Pharmaceutical and Biomedical Analysis 14, no. 8-10 (June 1996): 983–88. http://dx.doi.org/10.1016/0731-7085(95)01680-5.

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16

PACI, A. "Circulating endogenous digitalis-like factor(s) in essential hypertension." American Journal of Hypertension 9, no. 4 (April 1996): 69A. http://dx.doi.org/10.1016/0895-7061(96)81676-1.

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17

Lintlop, Steven P., Bill Durante, Fred A. Sunahara, and Amar K. Sen. "Digitalis-like biological activity in rat cerebellum." Biochemistry and Cell Biology 64, no. 10 (October 1, 1986): 1049–53. http://dx.doi.org/10.1139/o86-139.

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The cytosolic fraction of rat cerebellum possesses a factor(s) which is capable of inhibiting synaptosomal Na,K-ATPase activity, competing with [3H]ouabain binding to rat brain synaptosomes, and inducing positive inotropy in guinea pig atrial strips. These results demonstrate the existence of a ouabain-like principle in rat cerebella. The inhibitory activity of the factor was found to be partially thermolabile and diminished by a proteolytic agent, and the activity could be augmented by increasing concentrations of Mg2+, suggesting a regulatory mechanism for the endogenous digitalis-like principle.

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18

CLOIX, J. F., M. A. DEVYNCK, and P. MEYER. "Chemical and Clinical Studies of Endogenous Digitalis-Like Factor in Hypertension." Annals of the New York Academy of Sciences 488, no. 1 Membrane Path (December 1986): 217–27. http://dx.doi.org/10.1111/j.1749-6632.1986.tb46560.x.

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19

Shima, H., K. Kimura, K. Tsuda, K. Tanigawa, and I. Nishio. "Role of endogenous digitalis-like factor in peripheral sympathetic nervous system." Pathophysiology 1 (November 1994): 217. http://dx.doi.org/10.1016/0928-4680(94)90451-0.

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20

CRAMBERT, G., S. BALZAN, A. PACI, S. DECOLLOGNE, U. MONTALI, S. GHIONE, and L. G. LELIÈVRE. "Functional Characterization of an Endogenous Digitalis-Like Factor in Human Newborn Plasma." Annals of the New York Academy of Sciences 834, no. 1 Na/K-ATPase a (November 1997): 621–25. http://dx.doi.org/10.1111/j.1749-6632.1997.tb52332.x.

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21

Tatishvili, Nugzar I., Gayana V. Simonia, and Manana V. Khachidze. "Atrial natriuretic peptide and endogenous digitalis-like factor in chronic heart failure." Journal of Molecular and Cellular Cardiology 22 (May 1990): S98. http://dx.doi.org/10.1016/0022-2828(90)91817-q.

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22

Shilo, L., A. Pomeranz, M. Rathaus, J. Bernheim, and L. Shenkman. "Endogenous digoxin-like factor raises blood pressure and protects against digitalis toxicity." Life Sciences 44, no. 24 (January 1989): 1867–70. http://dx.doi.org/10.1016/0024-3205(89)90304-4.

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23

Yamada, Kaoru, Atsuo Goto, Chen Hui, and Tsuneaki Sugimoto. "Endogenous digitalis-like factor as a stimulator of endothelin secretion from endothelial cells." Biochemical and Biophysical Research Communications 172, no. 1 (October 1990): 178–83. http://dx.doi.org/10.1016/s0006-291x(05)80190-1.

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24

Ma, Jie, M. Sean Esplin, C. David Adair, Lorrie A. Mason, and Steven W. Graves. "Increasing Evidence for and Regulation of a Human Placental Endogenous Digitalis-Like Factor." Reproductive Sciences 19, no. 4 (February 16, 2012): 437–48. http://dx.doi.org/10.1177/1933719111424441.

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25

Yamada, K., A. Goto, and T. Sugimoto. "Effect of Endogenous Digitalis-Like Factor on Endothelin Secretion from Bovine Endothelial Cells." Journal of Cardiovascular Pharmacology 17 (1991): S163–164. http://dx.doi.org/10.1097/00005344-199100177-00045.

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26

Słabiak-Błaż, Natalia, and Grzegorz Piecha. "Endogenous Mammalian Cardiotonic Steroids—A New Cardiovascular Risk Factor?—A Mini-Review." Life 11, no. 8 (July 22, 2021): 727. http://dx.doi.org/10.3390/life11080727.

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The role of endogenous mammalian cardiotonic steroids (CTS) in the physiology and pathophysiology of the cardiovascular system and the kidneys has interested researchers for more than 20 years. Cardiotonic steroids extracted from toads or plants, such as digitalis, have been used to treat heart disease since ancient times. CTS, also called endogenous digitalis-like factors, take part in the regulation of blood pressure and sodium homeostasis through their effects on the transport enzyme called sodium–potassium adenosine triphosphatase (Na/K-ATPase) in renal and cardiovascular tissue. In recent years, there has been increasing evidence showing deleterious effects of CTS on the structure and function of the heart, vasculature and kidneys. Understanding the role of CTS may be useful in the development of potential new therapeutic strategies.

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27

Nakazaki, Atsuo, Keiko Hashimoto, Ai Ikeda, Takahiro Shibata, and Toshio Nishikawa. "De Novo Synthesis of Possible Candidates for the Inagami–Tamura Endogenous Digitalis-like Factor." Journal of Organic Chemistry 82, no. 17 (August 24, 2017): 9097–111. http://dx.doi.org/10.1021/acs.joc.7b01640.

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28

Deray, G., M. Rieu, M. A. Devynck, M. G. Pernollet, P. Chanson, J. P. Luton, and P. Meyer. "Evidence of an Endogenous Digitalis-like Factor in the Plasma of Patients with Acromegaly." New England Journal of Medicine 316, no. 10 (March 5, 1987): 575–80. http://dx.doi.org/10.1056/nejm198703053161003.

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29

Delva, Pietro, Marie-Aude Devynck, Maurizio Degan, Marie-Gabrielle Pernollet, Marco Carraroli, Claudio Capra, Anthony Steele, and Alessandro Lechi. "Plasma levels of an endogenous Na+–K+ pump inhibitor in relation to haemodynamic data in cardiopathic patients." Clinical Science 81, no. 1 (July 1, 1991): 23–29. http://dx.doi.org/10.1042/cs0810023.

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1. Despite the fact that numerous studies provide evidence for the existence of an endogenous inhibitor of the cell membrane Na+-K+ pump in plasma, little is known about the relationships between this factor and the main haemodynamic parameters. 2. In order to shed some light on this, we attempted to correlate haemodynamic parameters, measured during heart catheterization in a group of 22 cardiopathic subjects, with plasma digitalis-like activity levels, determined by two different procedures. 3. The ability of plasma to inhibit a human renal Na+-K+-ATPase showed an inverse correlation with cardiac index and a direct correlation with peripheral resistance. Plasma cross-reactivity with digoxin antibodies correlated directly with left atrial pressure. 4. These results furnish confirmation of a number of theoretical assumptions which attribute to the digitalis-like factor the ability to modify the contractility of the cardiovascular system.

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30

CHIBA, SHIGETOSHI, MIYOKO TSUKADA, YOSHIHIKO KATSUYAMA, AKIHIRO TADA, and HIROSHI ZENDA. "Potent vasoconstrictor responses to endogenous digitalis-like factor of isolated, perfused dog intermediate auricular arteries." Tohoku Journal of Experimental Medicine 151, no. 3 (1987): 359–62. http://dx.doi.org/10.1620/tjem.151.359.

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31

DORIS, PETER A. "Immunological Evidence that the Adrenal Gland Is a Source of an Endogenous Digitalis-Like Factor*." Endocrinology 123, no. 5 (November 1988): 2440–44. http://dx.doi.org/10.1210/endo-123-5-2440.

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32

Castañeda-Hernández, Gilberto. "Evidence for the existence of the same endogenous digitalis-like factor in several mammalian species." Comparative Biochemistry and Physiology Part C: Comparative Pharmacology 94, no. 1 (January 1989): 49–53. http://dx.doi.org/10.1016/0742-8413(89)90143-6.

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33

Bagrov, Alexei Y., Natalia I. Roukoyatkina, Olga V. Federova, Alexander G. Pinaev, and Maria V. Ukhanova. "Digitalis-like and vasoconstrictor effects of endogenous digoxin-like factor(s) from the venom of Bufo marinus toad." European Journal of Pharmacology 234, no. 2-3 (April 1993): 165–72. http://dx.doi.org/10.1016/0014-2999(93)90950-m.

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34

Goto, A., K. Yamada, and M. Omata. "Quabain-like compound as an endogenous digitalis-like factor and as a regulator of blood pressure and electrolyte homeostasis." Pathophysiology 1 (November 1994): 215. http://dx.doi.org/10.1016/0928-4680(94)90448-0.

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35

Soszynski, P., J. Slowinska-Srzednicka, A. Kasperlik-Zaluska, and S. Zgliczynski. "Endogenous natriuretic factors: atrial natriuretic hormone and digitalis-like substance in Cushing's syndrome." Journal of Endocrinology 129, no. 3 (June 1991): 453–58. http://dx.doi.org/10.1677/joe.0.1290453.

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ABSTRACT In order to investigate the effect of chronic hypercortisolaemia on endogenous natriuretic factors (atrial natriuretic hormone (ANH) and the Na+/K+ pump inhibitor) digitalis-like substance (DLS), and their relation to hypertension, 28 patients with pituitary-or adrenal-dependent Cushing's syndrome and six patients on high-dose prednisone treatment were studied. Plasma ANH levels were increased in patients with Cushing's syndrome (36·0±1·4 (s.e.m.) ng/l) compared with those in healthy controls (28·6±1·3 ng/l, P <0·01). In prednisone-treated patients, ANH levels (43·8±4·5 ng/l) were higher than those in patients with Cushing's syndrome and in controls (P <0·05 and P <0·01 respectively). DLS measured by radioimmunoassay and binding of [3H]ouabain to erythrocytes was not altered in patients with hypercortisolaemia. Slightly decreased DLS activity in the erythrocyte 86Rb uptake inhibition assay was found in patients with Cushing's syndrome (52·9±2·7%) compared with that in controls (60·9±1·8%, P <0·02). With the exception of cortisol (r = 0·52, P<0·01), none of the other factors determined correlated with the mean arterial pressure in patients with Cushing's syndrome. Thus, a chronic excess of endogenous and exogenous glucocorticoids increases plasma levels of ANH, but does not substantially influence DLS activity or plasma levels. Neither natriuretic factor is directly related to hypertension in Cushing's syndrome. Journal of Endocrinology (1991) 129, 453–458

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36

Adair, C. David, Vardaman Buckalew, Steven W. Graves, Nikhil Chauhan, and Garrett Lam. "T10.5 Digoxin Immune Fab treatment for severe preclampsia; relationship between response and baseline endogenous digitalis-like factor." Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health 1 (October 2010): S21. http://dx.doi.org/10.1016/s2210-7789(10)60093-1.

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37

DORIS, P. A., and D. M. STOCCO. "An Endogenous Digitalis-Like Factor Derived from the Adrenal Gland: Studies of Adrenal Tissue from Various Sources." Endocrinology 125, no. 5 (November 1989): 2573–79. http://dx.doi.org/10.1210/endo-125-5-2573.

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38

Nakamura, T., S. Ichikawa, K. Sato, Y. Tajima, H. Fujita, and K. Murata. "Time-Related Alterations in an Endogenous Digitalis-Like Factor in the Development of Doca-Salt Hypertension in Rats." Clinical and Experimental Hypertension. Part A: Theory and Practice 9, no. 11 (January 1987): 1733–44. http://dx.doi.org/10.3109/10641968709158969.

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39

Kitano, Shoichi, Shigeto Morimoto, Akira Nishibe, Keisuke Fukuo, Atushi Hirotani, Takeshi Nakahashi, Osamu Yasuda, and Toshio Ogihara. "Exogenous Ouabain Is Accumulated in the Adrenals and Mimics the Kinetics of Endogenous Digitalis-like Factor in Rats." Hypertension Research 21, no. 1 (1998): 47–56. http://dx.doi.org/10.1291/hypres.21.47.

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40

Bernini, G. "Endogenous Digitalis-Like Factor and Ouabain Immunoreactivity in Adrenalectomized Patients and Normal Subjects After Acute and Prolonged Salt Loading." American Journal of Hypertension 11, no. 1 (January 1998): 1–7. http://dx.doi.org/10.1016/s0895-7061(97)00306-3.

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41

Reznik, Vitaly A., Dmitry O. Ivanov, Nikolaj N. Ruhlyada, Natal’ya I. Tapilskaya, and Ivan A. Ershov. "The importance of antiangiogenic substances endoglin and sFLT-1, as well as endogenous digitalis-like factor marinobufagenin in the pathogenesis of preeclampsia." Pediatrician (St. Petersburg) 11, no. 1 (April 23, 2020): 5–12. http://dx.doi.org/10.17816/ped1115-12.

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Objective. Establish the relationship between the action of antiangiogenic factors sFLT-1 and endoglin, as well as marinobufagenin in the formation of symptoms of preeclampsia in the clinic and experiment. Materials and methods. In the first experimental phase, preeclampsia-like state was simulated in pregnant rats, the changes in the content of substances reflected in the target tissues were studied, as well as the effect on their concentrations of anti-marinobufagenin antibodies. In the second (clinical) phase, changes in the content of sFlt-1 and endoglin-1 in placental tissues, as well as marinobufagenin in blood plasma and activity of Na+/K+-ATPase of erythrocytes in pregnant women with preeclampsia were studied. Results. In rats, an increase in systolic blood pressure, and marinobufagenin plasma levels was observed during the formation of a preeclampsia-like condition. Administration of antibodies to marinobufagenin caused a decrease in blood pressure. Found that during the formation of a preeclampsia-like condition, there is an increase in the content of sFlt-1 in the placenta and thoracic aorta and endoglin in the placenta. In patients with preeclampsia, it was found that the increase in blood pressure occurs against the background of an increase in the content of marinobufagenin in blood plasma, as well as a decrease in the activity of Na+/K+-ATPase of erythrocytes. The formation of preeclampsia is accompanied by a significant increase in the level of antiangiogenic factors endoglin and sFlt-1 in the placenta. Summary. In patients with preeclampsia, the development of clinical symptoms is accompanied by an increase in the placental tissues of the content of antiangiogenic factors endoglin and sFlt-1 and the content of marinobufagenin in blood plasma. The obtained data are confirmed by the results of an experiment performed on pregnant rats with modeling of preeclampsia-like condition.

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Graves, S. W., M. Hopoate-Sitake, A. Johnston, V. Buckalew, G. Lam, L. Mason, and D. Adair. "PP087. Deep trial secondary analysis: Digoxin immune fab fragment treatment has additional benefits in endogenous digitalis-like factor positive preeclamptic women." Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health 2, no. 3 (July 2012): 287–88. http://dx.doi.org/10.1016/j.preghy.2012.04.198.

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Lam, Garrett K., Moana Hopoate-Sitake, C. David Adair, Vardaman M. Buckalew, Donna D. Johnson, David F. Lewis, Christopher J. Robinson, George R. Saade, and Steven W. Graves. "Digoxin antibody fragment, antigen binding (Fab), treatment of preeclampsia in women with endogenous digitalis-like factor: a secondary analysis of the DEEP Trial." American Journal of Obstetrics and Gynecology 209, no. 2 (August 2013): 119.e1–119.e6. http://dx.doi.org/10.1016/j.ajog.2013.04.010.

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Graves, Steven W., J. Paul Eder, Susan M. Schryber, Kiran Sharma, Anne Brena, Karen H. Antman, and William P. Peters. "Endogenous Digoxin-Like Immunoreactive Factor and Digitalislike Factor Associated with the Hypertension of Patients Receiving Multiple Alkylating Agents as Part of Autologous Bone Marrow Transplantation." Clinical Science 77, no. 5 (November 1, 1989): 501–7. http://dx.doi.org/10.1042/cs0770501.

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1. Hypertension is a complication of autologous bone marrow transplantation when therapy includes multiple alkylating agents. We have sought to identify the factors underlying this hypertension. We measured weight, serum creatinine, plasma renin activity, aldosterone and digoxin-like immunoreactive factor (DL1F), by digoxin radioimmunoassay, in 18 patients. Plasma catecholamines were also measured in five patients. 2. Of the 18 patients studied, 15 became hypertensive. The variable most consistently associated with these individuals' hypertension was DLIF activity which was increased in 14 of the 15 hypertensive patients (P = 0.055, Fisher exact test). Serum creatinine was increased at some point in seven of the 15 hypertensive patients, weight was increased in five and plasma renin activity and aldosterone were increased in one. Catecholamines were not increased in any of the five patients in which they were measured. 3. The association between changes in mean arterial pressure (MAP) and changes in DL1F for the group as a whole was assessed by analysing one data pair per patient, representing the maximal MAP. This correlation was significant (r = 0.75, P = 0.001). 4. Within individual patients, changes in MAP and changes in serum DLIF concentrations were significantly correlated (r > 0.50, P < 0.05) in six of 15 hypertensive patients. 5. Digitalis-like factor (DLF) was measured by inhibition of (Na+,K+)-adenosine 5′-triphosphatase in five patients and DLF and DLIF were significantly correlated (r = 0.81, P = 0.0001). DLF and MAP were also significantly correlated (r = 0.59, P = 0.002). 6. This represents the first longitudinal study of the relationship between DLIF and blood pressure in hypertensive individuals, and the results suggest that DLIF may contribute to the increased blood pressure in some of these subjects.

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De Angelis, C., and G. T. Haupert. "Hypoxia triggers release of an endogenous inhibitor of Na+-K+-ATPase from midbrain and adrenal." American Journal of Physiology-Renal Physiology 274, no. 1 (January 1, 1998): F182—F188. http://dx.doi.org/10.1152/ajprenal.1998.274.1.f182.

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An endogenous inhibitor of Na+-K+-ATPase has been isolated from bovine hypothalamus and human plasma and structurally characterized as an isomer of the plant cardiac glycoside, ouabain (A. A. Tymiak, J. A. Norman, M. Bolgar, G. C. DiDonato, H. Lee, W. L. Parker, L.-C. Lo, N. Berova, K. Nakanishi, E. Haber, and G. T. Haupert, Jr. Proc. Natl. Acad. Sci. USA 90: 8189–8193, 1993; N. Zhao, L.-C. Lo, N. Berova, K. Nakanishi, J. H. Ludens, and G. T. Haupert, Jr. Biochemistry 34: 9893–9896, 1995). This hypothalamic inhibitory factor (HIF) acts on cardiovascular and renal tissues consistent with physiological regulation in vivo. Stimuli for the release of HIF from tissue are unknown. Hypoxia may be a stimulus for the elaboration of digitalis-like activity in humans, and high NaCl concentration in central nervous system stimulates ouabain-like activity in animals. We examined the ability of low O2 tension in vivo and in vitro to stimulate HIF release from midbrain and adrenal tissues in Wistar rats. In both tissues, hypoxia stimulated a remarkable release of an inhibitor cochromatographing with HIF, and this release was enhanced by 300 mM NaCl. Plasma from hypoxic rats also showed increased levels of the purified inhibitory activity. We conclude that hypoxia is a potent stimulus for the release of HIF or HIF-like activity and discuss the possibility that an Na+-K+-ATPase inhibitor could be involved in energy-conserving cellular adaptive responses to hypoxic or ischemic insult through ATP conservation.

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Komjáti, Katalin, Joel H. Greenberg, Martin Reivich, and Peter Sándor. "Interactions between the Endothelium-Derived Relaxing Factor/Nitric Oxide System and the Endogenous Opiate System in the Modulation of Cerebral and Spinal Vascular CO2 Responsiveness." Journal of Cerebral Blood Flow & Metabolism 21, no. 8 (August 2001): 937–44. http://dx.doi.org/10.1097/00004647-200108000-00006.

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The role of the L-arginine-nitric oxide (NO) system, the role of the endogenous morphine-like substances (endorphins), and the possible interaction between these two systems in the modulation of regional cerebral and spinal CO2 responsiveness was investigated in anesthetized, ventilated, normotensive, normoxic cats. Regional cerebral blood flow was measured with radiolabeled microspheres in hypocapnic, normocapnic, and hypercapnic conditions in nine individual cerebral and spinal cord regions. General opiate receptor blockade by 1 mg/kg naloxone intravenously alone or NO synthase blockade by 3 mg/kg Nω-nitro-L-arginine-methyl ester (L-NAME) intravenously alone caused no changes in regional CO2 responsiveness. Combined administration of these two blocking agents in the very same doses, however, resulted in a strong potentiation, with a statistically significant reduction of the CO2 responsiveness observed. Separation of the blood flow response to hypercapnia and hypocapnia indicates that this reduction occurs only during hypercapnia. Specific μ and δ opiate receptors were blocked by 0.5 mg kg−1 IV β-funaltrexamine and 0.4 mg kg−1 IV naltrindole, respectively. The role of specific μ and δ opiate receptors in the NO–opiate interaction was found to be negligible because neither μ nor δ receptor blockade along with simultaneous NO blockade were able to decrease CO2 responsiveness. The current findings suggest a previously unknown interaction between the endothelium-derived relaxing factor/nitric oxide (EDRF/NO) system and the endogenous opiate system in the cerebrovascular bed during hypercapnic stimulation, with the phenomenon not mediated by μ or δ opiate receptors.

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Karnia, Mateusz Jakub, Dorota Myślińska, Katarzyna Patrycja Dzik, Damian Józef Flis, Magdalena Podlacha, and Jan Jacek Kaczor. "BST Stimulation Induces Atrophy and Changes in Aerobic Energy Metabolism in Rat Skeletal Muscles—The Biphasic Action of Endogenous Glucocorticoids." International Journal of Molecular Sciences 21, no. 8 (April 17, 2020): 2787. http://dx.doi.org/10.3390/ijms21082787.

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(1) The primary involvement in stress-induced disturbances in skeletal muscles is assigned to the release of glucocorticoids (GCs). The current study aims to investigate the impact of the biphasic action of the chronic stress response (CSR) induced by the electrical stimulation of the bed nucleus of the stria terminalis (BST) effects on muscle atrophy and aerobic energy metabolism in soleus (SOL) and extensor digitorum longus (EDL) muscles. (2) Male Wistar rats (n = 17) were used. The rats were divided randomly into three groups: the BST two weeks (ST2), four weeks (ST4), and the sham (SHM) electrically stimulated group. The plasma corticosterone (CORT) and irisin concentration were measured. Glucocorticoid and mineralocorticoid receptors (GR and MR), 11β-hydroxysteroid dehydrogenase type 1 and 2 (HSD11B1 and HSD11B2), atrogin-1, and insulin-like growth factor-1 (IGF-1) level were determined in SOL and EDL muscles. Citrate synthase (CS) activity was measured in both muscles. (3) We found elevated plasma concentration of CORT and irisin, raised the level of GR in SOL muscle, and the higher level of MR in both muscles in the ST4 group. The level of HSD11B1 was also higher in the ST4 group compared to the SHM group. Moreover, we observed increased activity of CS in SOL. (4) We suggest that biphasic action of the glucocorticoid induced by the CSR occurs and causes dysregulation of proteins involved in muscle atrophy and aerobic energy metabolism. Our findings potentially contribute to a better understanding of the mechanisms by which GCs and the CSR may regulate muscle atrophy and energy preservation of the red muscle.

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Sakakibara, Masayuki, and Aki Ogawa Uchida. "Syntheses of (14β,15β,16β,17α)- and (14β,15α,16α,17α)-1,3,5(10)-Estratriene-2,3,14,15, 16,17-hexaols, Possible Candidates for the Inagami—Tamura Endogenous Digitalis-like Factor, and Their Activity." Bioscience, Biotechnology, and Biochemistry 60, no. 3 (January 1996): 405–10. http://dx.doi.org/10.1271/bbb.60.405.

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Ahmad, Ashfaq, Sara Dempsey, Zdravka Daneva, Maleeha Azam, Ningjun Li, Pin-Lan Li, and Joseph Ritter. "Role of Nitric Oxide in the Cardiovascular and Renal Systems." International Journal of Molecular Sciences 19, no. 9 (September 3, 2018): 2605. http://dx.doi.org/10.3390/ijms19092605.

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The gasotransmitters are a family of gaseous signaling molecules which are produced endogenously and act at specific receptors to play imperative roles in physiologic and pathophysiologic processes. As a well-known gasotransmitter along with hydrogen sulfide and carbon monoxide, nitric oxide (NO) has earned repute as a potent vasodilator also known as endothelium-derived vasorelaxant factor (EDRF). NO has been studied in greater detail, from its synthesis and mechanism of action to its physiologic, pathologic, and pharmacologic roles in different disease states. Different animal models have been applied to investigate the beneficial effects of NO as an antihypertensive, renoprotective, and antihypertrophic agent. NO and its interaction with different systems like the renin–angiotensin system, sympathetic nervous system, and other gaseous transmitters like hydrogen sulfide are also well studied. However, links that appear to exist between the endocannabinoid (EC) and NO systems remain to be fully explored. Experimental approaches using modulators of its synthesis including substrate, donors, and inhibitors of the synthesis of NO will be useful for establishing the relationship between the NO and EC systems in the cardiovascular and renal systems. Being a potent vasodilator, NO may be unique among therapeutic options for management of hypertension and resulting renal disease and left ventricular hypertrophy. Inclusion of NO modulators in clinical practice may be useful not only as curatives for particular diseases but also for arresting disease prognoses through its interactions with other systems.

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"Digitalis-like and vasoconstrictor properties of endogenous digoxin-like factor (EDLF) from Bufo marinus toad." Journal of Molecular and Cellular Cardiology 24 (May 1992): 259. http://dx.doi.org/10.1016/0022-2828(92)90803-8.

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