Dissociation of digoxin-like immunoreactivity and Na+,K+-ATPase inhibitory activity in rat plasma

Yamada, Kaoru; Goto, Atsuo; Ishii, Masao; Yoshioka, Masanori; Sugimoto, Tsuneaki

doi:10.1007/bf01939897

Cited by 18 publications

(9 citation statements)

References 18 publications

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“…The digi talis group of compounds usually has digoxin like immunoreactivity (26), but in the present experiment, the immunoreactivity to digoxin antibody of ouabain was significantly lower than that of digoxin, although those Na+,K+ ATPase inhibitory activities were not differ ent. These results may support the observation of Yamada et al (14) in which the Na+,K+ ATPase inhibitory activity dissociates from the digoxin-like immunoreactivity. Therefore, the possibility that endogenously synthesized oua bain is contained in the plasma extract still re mains.…”

Section: Discussionsupporting

confidence: 92%

“…One of the possible causes of the dif ference may be that the present plasma extract does not contain endogenously synthesized digoxin even if the substance is present in the plasma; that is, the substances determined are different. In addition, it has been reported that there are some digoxin-like immunoreac tive factors without Na+,K+-ATPase inhibitory activity (14,28). Another cause may be the dilution of the ouabain-like substance inhibit ing Na+,K±ATPase by the larger circulating blood volume in the NP group than in the N group.…”

Section: Discussionmentioning

confidence: 99%

“…However, different results have been re ported: some reports indicated that the level of the substance in PIH was higher than that in NP (8 -10), but others found that it was lower (11,12) or comparable to the level in NP (13). Digoxin-like immunoreactive sub stances in unpurified material are not neces sarily always the same as the substances with Na+,K+-ATPase inhibitory activity (14), but only one of the studies determined the Na+,K+-ATPase inhibitory activities of the substances (8). Unfortunately, even when the enzyme activity was assayed (4,8), the assay mixtures employed contained a high K+ con centration; under such a condition, the observed inhibitory activity would include the non-specific (i.e., non ouabain-like) inhibitory activity (15).…”

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confidence: 97%

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Ouabain-Like Na+,K+-ATPase Inhibitory Activity of a Plasma Extract in Normal Pregnancy and Pregnancy Induced Hypertension.

et al. 1991

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ABSTRACT-To estimate the participation of a Na+,K±ATPase-inhibiting plasma foctor in pregnancy induced hypertension (PIH), the inhibitory activity and the char acteristics of plasma extract eluted with ethanol through a C8 column were examined in normotensive non-pregnant women (N) and women with normal pregnancy (NP) and PIH. There were no differences among the 3 groups in the Na+,K+-ATPase activ ity of erythrocyte ghosts. The heat and acid-stable plasma extract dose-dependently inhibited Na+,K+-ATPase activity with a pattern similar to that of ouabain, but differ ent from that of vanadate. The inhibitory activity of plasma extract was not influenced by polyclonal digoxin antibody which almost completely prevented digoxin-induced in hibition and slightly but significantly reduced the ouabain-induced one. The results in dicate that the plasma extract has ouabain-like inhibitory activity on Na+,K+-ATPase and that it is not endogenously synthesized digoxin itself, but a substance differing in structure from digoxin. Furthermore, the ouabain-like Na+,K+-ATPase inhibitory activity in NP plasma was significantly lower than that in PIH plasma, which was simi lar to that in N plasma. There were significant relationships between the ouabain-like Na+,K±ATPase inhibitory activities in plasma and the diastolic and systolic blood pressures in NP and PIH groups. The results suggest that the lower ouabain-like Na+,K+-ATPase inhibitory activity in plasma probably participates in maintaining the blood pressure within the normal range during pregnancy and its failure may be in volved in the genesis of PIH.A hypothesis that plasma-volume expansion associated with salt retention leads to the re lease of a circulating Na+,K+-ATPase inhibi tor and that the inhibitor causes not only natri uresis but also vascular contraction resulting in hypertension has been proposed (1, 2). A canine plasma extract that inhibits Na+,K+ ATPase released by volume expansion has been observed to have digoxin-like immuno reactivity (3), and the endogenous digitalis like substance increases sensitivity to the vaso constrictive effects of norepinephrine and angiotensin (4). Hamlyn et al. (5) showed that the Na+,K±ATPase inhibitory activity of a plasma substance was related to the high blood pressure in subjects with essential

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 97%

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Ouabain-Like Na+,K+-ATPase Inhibitory Activity of a Plasma Extract in Normal Pregnancy and Pregnancy Induced Hypertension.

et al. 1991

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“…Comparison with our findings is problematic as Yamada et al studied much younger animals weighing about 130 g after 15 days of ACTH treatment, whereas we measured EDLF after 8 days of ACTH administration in rats weighing about 380 g. We hypothesize that the discrepancy in the results of these two experiments reflects a different time course of the changes in the two digitalis-like factors. Such dissociation between EDLF levels measured by different methods has been recently reported in volumeexpanded rats 30 and dogs, 31 and exemplifies the heterogeneity of EDLF.31 Moreover, sodium balance may be different on days 8 and 15 of ACTH treatment. In accord with previous findings, 1,2,23 plasma Na in ACTH-treated rats in our experiment was increased (indicating sodium retention), whereas no such difference was observed on day 15 of ACTH hypertension.…”

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confidence: 99%

Plasma Marinobufagenin-Like and Ouabain-Like Immunoreactivity in Adrenocorticotropin-Treated Rats

Федорова

Anderson

Bagrov

1998

American Journal of Hypertension

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Recently, an endogenous digitalis-like factor (EDLF) was shown to be stimulated in corticotropin (ACTH) hypertension in the rat. We have shown that mammalian plasma contains a vasoconstrictor Na,K-ATPase inhibitor, which cross-reacts with an antibody to amphibian EDLF, marinobufagenin. In the present experiment, the effect of 8 days of intramuscular ACTH treatment (0.5 mg/kg/day) of male Fisher 344؋ ؋NB rats on blood pressure, plasma ouabain-like and marinobufagenin-like immunoreactivity, and on the activity of Na,KATPase in aortic sarcolemma were studied.The C hronic administration of ACTH has been reported to raise the blood pressure of various mammalian species, including humans and rats.1,2 The hypertensinogenic effects of ACTH administration are dependent on the adrenal cortex and could be prevented by adrenalectomy.1,3 ACTH-induced hypertension has been attributed to the action of various adrenocorticosteroids, including aldosterone and progesterone derivatives in sheep, 4 cortisol in humans, 5 and corticosterone in the rat. 6 Several lines of evidence indicate the existence of digitalis-like immunoreactive endogenous inhibitors of Na,K-ATPase in mammalian tissues.7,8 Endogenous digitalis-like factors (EDLF) are believed to play an important role in sodium homeostasis and to contribute to several forms of human and animal hypertension.9,10 The adrenal cortex has been shown to be one of the major sources of EDLF in mammals.11,12 Endogenous ouabain was the first EDLF to be purified from human plasma, 13 and recent evidence indicates that Recently, we showed that a bufodienolide Na,KATPase inhibitor, marinobufagenin, elicits vasoconstrictor and Na,K-pump inhibitory effects in rat aorta. 19 Subsequently, it was established that mammalian plasma contains marinobufagenin-like immunoreactive material, which is responsive to saline volume expansion and is chromatographically indistinguishable from amphibian marinobufagenin. 15,20,21 When effects of marinobufagenin and ouabain were compared in membrane fractions prepared from rat aortae, marinobufagenin preferentially inhibited Na,KATPase in vascular smooth muscle membranes (␣-1 isoform), whereas ouabain demonstrated higher affinity toward Na,K-ATPase from vascular nerve endings (␣-3 isoform). 22In 1994, Li et al 23 showed that hypertension in rats occurring after 8 days of ACTH administration was associated with an increase in plasma digoxin-like immunoreactivity. Subsequently, Yamada et al 24 showed that ACTH treatment of rats for 15 days increased blood pressure and plasma levels and urinary release of an ouabain-like immunoreactive material.Recent observations suggest that mammalian plasma contains several substances with the ability to inhibit the sodium pump and to interact with digitalis antibodies, 8,25 and that different digoxin antibodies demonstrate wide variability in their capacity to detect EDLF. 7,26 The purpose of the present study was to investigate whether ACTH hypertension in the rat is associated with increased plasma levels of marinobufagenin-l...

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“…Many steroids give false-pos itive results for digoxin, as do many lipids and bile acids. Recent findings indicate the dissociation of digoxin-like immunoreactivity from digitalis-like biological activity [3][4][5].We have recently purified to homogeneity two distinct digitalis-like factors from human urine based on [JH]ouabain displacing activity from intact human erythrocytes [6,7]. The polar compound was eluted off the C18 reverse phase column with 18% acetonitrile and cross-reacted very weakly with specific antidigoxin antibody.…”

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confidence: 99%

Does Digoxin-Like Immunoreactivity Really Represent the Natriuretic Hormone?

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Yamada²,

Ishii³

et al. 1990

Nephron

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Dissociation of digoxin-like immunoreactivity and Na+,K+-ATPase inhibitory activity in rat plasma

Cited by 18 publications

References 18 publications

Ouabain-Like Na+,K+-ATPase Inhibitory Activity of a Plasma Extract in Normal Pregnancy and Pregnancy Induced Hypertension.

Ouabain-Like Na+,K+-ATPase Inhibitory Activity of a Plasma Extract in Normal Pregnancy and Pregnancy Induced Hypertension.

Plasma Marinobufagenin-Like and Ouabain-Like Immunoreactivity in Adrenocorticotropin-Treated Rats

Does Digoxin-Like Immunoreactivity Really Represent the Natriuretic Hormone?

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