Increased circulating levels of an endogenous digoxin-like factor in hypertensive monkeys.

Gruber, Kenneth A.; Rudel, Lawrence L.; Bullock, Bill C.

doi:10.1161/01.hyp.4.3.348

Cited by 95 publications

(18 citation statements)

References 38 publications

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“…Recently, several reports have appeared suggesting the presence of endogenous digitalis-like substances in various organs or body fluids (5)(6)(7)(8)(9)(10)(11)(12)(13). Besides the presence of DLIS, DTLIS was detected in amniotic fluid or cord blood in our study.…”

Section: Discussionsupporting

confidence: 58%

Digoxin- and Digitoxin-Like Immunoreactive Substances in Amniotic Fluid, Cord Blood, and Serum of Neonates

et al. 1986

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ABSTRAm. Using four different digoxin kits, it was disclosed that the majority of various samples including amniotic fluid, cord blood, and serum from neonates contained substantial levels of digoxin-like immunoreactive substance. The differences in data seemed to be due to the range of epitopes which are recognized by antidigoxin antiserum. The day-to-day studies on sera serially obtained from infants at birth to 48 days old revealed that the level of the substance (0.31 f 0.12 ng/ml) in sera of the l-dayold neonates rapidly declined to the level of 0.1 ng/ml by the 2nd postnatal wk and thereafter gradually declined. The immunological specificity and accuracy of the detection of digoxin-like immunoreactive substance was confirmed by a sample dilution test, a recovery test for standard digoxin, and an absorption test with antidigoxin antiserum. The amniotic fluid and cord blood also contained Recent reports (1-3) renewed our attention toward the falsepositive digoxin measurements in the plasma of premature infants (4). From the clinical viewpoint, these observations raise some important questions. The first question is whether the falsepositive digoxin measurement really indicates the presence of a DLIS which leads to an erroneous judgment about the level of digoxin in monitoring of neonatal samples. The second question is whether there is any similarity in biochemical specificity between DLIS and the so-called "ouabain-like substances" detected in other organs or body fluids (5-13). It seems that previous reports (1-3) have not yet provided substantial evidence for their conclusion that the substance is not a product of technical or nonimmunological false positivity. Therefore, in this communication, we tried to confirm the previous findings using Received September 6, 1984; accepted August 19, 1985. Address for correspondence Hiroyoshi Ebara, M.D., Department of Pediatrics, Gunma University School of Medicine, 3-39-22 Showa-machi, Maebashi-shi, Gunma-ken, Japan. amniotic fluid, cord blood, and serum specimen from neonates and also to evaluate immunological specificity of the reaction and presence of a DTLIS. MATERIALS AND METHODSThirty-one amniotic fluid and 53 cord blood samples were obtained from mothers who had not received any digitalis glycosides during pregnancy and labor. One hundred eleven sera were also obtained from 23 neonates over 35-wk gestational age who were delivered from healthy mothers who had not been on digitalis therapy. The mean and range of birth weight of the neonates were 3264 g and 20 16-4420 g, respectively. The investigation was approved by the ethical committee of the hospital and informed parental consent was obtained for blood sampling. All samples were stored at -20" C in separate small quantities to avoid unnecessary freezing and thawing, and analyzed at various intervals, always within 30 days of collection.For the detection of DLIS, one EIA kit and three RIA kits available in Japan were used: kit A (Markit Digoxin, DainipponSeiyaku, Osaka, Japan); kit B (Amerlex Digoxin RIA k...

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Section: Discussionsupporting

confidence: 58%

Digoxin- and Digitoxin-Like Immunoreactive Substances in Amniotic Fluid, Cord Blood, and Serum of Neonates

et al. 1986

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“…Previous reports indicated that plasma NKI is active i) to inhibit Na, K-ATPase (Gruber et al 1980(Gruber et al , 1982.…”

Section: Discussionmentioning

confidence: 98%

A plasma inhibitor of sodium and potassium activated adenosine triphosphatase in patients with essential hypertension.

Toriyabe

Miura

Kimura

et al. 1988

Tohoku J. Exp. Med.

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“…9 Poston et al 42 have recently reported the presence of a circulating inhibitor of the ouabain sensitive 22 Na efflux of red and white cells in humans with essential hypertension. In addition, a circulating ouabain-like factor has been demonstrated in dogs with one-kidney one-wrapped hypertension, and in rats with reduced renal mass-saline hypertension.…”

Section: Discussionmentioning

confidence: 99%

Evidence for a vascular sensitizing factor in plasma of saline-loaded dogs.

Plunkett¹,

Hutchins²,

Gruber³

et al. 1982

Hypertension

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SUMMARY This study investigates whether plasma extracts previously demonstrated to have natriuretic and antinatriferic activity have effects on vascular reactivity of rat cremaster arterioles. Plasma from hydropenic and saline-loaded dogs was subjected to Diafiltration, and eluted on a strong cation exchange column (SCX). The effects of intraarterial injections of various column fractions on constrictor responses to repeated injections of 33.3 ng of norepinephrine (NE) were used to indicate changes in vascular responsiveness in third order cremaster arterioles. SCX fraction I (void volume) from saline-loaded dogs (FI-S) caused an increase in constrictor response to NE of 101 %. Increased vascular responsiveness peaked at 40 minutes and remained significantly elevated (p < 0.05) for 130 minutes. Fraction I from plasma of hydropenic dogs (FI-H) and fraction III from plasma of salineloaded dogs (FIII-S) did not increase vascular responsiveness to NE. FI-S shifted the dose response curves for NE, arginine vasopressin, and angiotensin II parallel and to the left relative to control by a factor of 3.05-, 2.95-, and 5.63-fold, respectively, at the 50% constrictor dose. Systemic injections of FI-S, but not FI-H, caused a 10 mm Hg rise in blood pressure at 50 minutes, and blood pressure was significantly elevated for 30 to 90 minutes after injection (p < 0.01).These data demonstrate a vascular-sensitizing factor in FI-S. The factor appears in the same chromatographic fraction previously demonstrated to contain natriuretic, antinatriferic, and digoxin-like activity. The correlation of these activities with salt loading suggests they are due to the same substance, which may be the putative natriuretic hormone. 3 demonstrated that hypertension could be transferred from a genetically salt-sensitive rat (S rat) to a salt-resistant rat (R rat) when both were joined in a parabiotic union and fed salt. Based on these experiments, Dahl et al. suggested that salt-induced hypertension might be caused by a low molecular weight,

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Increased circulating levels of an endogenous digoxin-like factor in hypertensive monkeys.

Cited by 95 publications

References 38 publications

Digoxin- and Digitoxin-Like Immunoreactive Substances in Amniotic Fluid, Cord Blood, and Serum of Neonates

Digoxin- and Digitoxin-Like Immunoreactive Substances in Amniotic Fluid, Cord Blood, and Serum of Neonates

A plasma inhibitor of sodium and potassium activated adenosine triphosphatase in patients with essential hypertension.

Evidence for a vascular sensitizing factor in plasma of saline-loaded dogs.

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