Circulating factor with ouabain-like immunoreactivity in patients with primary aldosteronism

Masugi, Fuminori; Ogihara, Toshio; Hasegawa, T.; Tomii, Akiko; Nagano, Masahiro; Higashimori, Koichi; Kumahara, Keiichiro; Terano, Yoshitake

doi:10.1016/0006-291x(86)90939-3

Cited by 51 publications

(21 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previously, an enzyme-linked immunosorbent-assay (ELISA) method gave plasma ouabain concentrations of 138 pmol/l (Hamlyn et al 1991). In other studies even greater concentrations have been reported, but the identity of the immunoreactivity was not studied (Masugi et al 1986, Harris et al 1991, Gottlieb et al 1992, Rossi et al 1995. In a more recent radioimmunoassay study, plasma ouabain concentrations in healthy volunteers (sex not stated) were found to be 25 pmol/l and the immunoreactivity eluted in HPLC in the same way as ouabain .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Radioimmunoassay of plasma ouabain in healthy and pregnant individuals

Vakkuri

Árnason²,

Pouta³

et al. 2000

Journal of Endocrinology

View full text Add to dashboard Cite

Ouabain was recently isolated from human plasma, bovine hypothalamus and bovine adrenal in attempts to identify endogenous substances inhibiting the cell membrane sodium pump. A number of radioimmunoassays have been developed in order to study the clinical significance of ouabain. The results have been controversial with regard to the presence and chemical nature of plasma ouabainlike immunoreactivity. We have now measured ouabain in healthy and pregnant individuals using solid-phase extraction of plasma samples followed by a new radioimmunoassay with the extraordinary sensitivity of at least 2 fmol/tube (5 pmol/l). Plasma extracts, a previously isolated human plasma ouabain-like compound and bovine hypothalamic inhibitory factor displaced the tracer in parallel and eluted identically with ouabain in highperformance liquid chromatography. Plasma ouabain immunoreactivity was found to be much lower than reported previously: 12·6 1·3 pmol/l in healthy men (mean .., n=20) and 9·4 0·7 pmol/l in women (n=14). In pregnant women (n=28) plasma ouabain concentration was 16·3 4·0 pmol/l during the first trimester, 18·8 4·3 pmol/l during the second trimester and 24·3 4·0 pmol/l during the third trimester (all P<0·01 compared with non-pregnant women). Plasma ouabain 3-5 days after the delivery was 13·6 1·1 pmol/l (n=10, P<0·05-0·01 compared with second and third trimesters). The pregnancy-related changes in the plasma concentrations of ouabain resembled those of cortisol. Therefore cortisol was measured from the same plasma samples and a significant positive correlation was found (r=0·512, P=0·006). The similar profiles of plasma ouabain and cortisol during pregnancy and their rapid decreases postpartum are consistent with the adrenal cortical origin of ouabain and also show that the secretions of these hormones are possibly under the control of same factors.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Ouabain was coupled to bovine thyroglobulin using the periodination and sodium cyanoborohydride method according to Masugi et al (1986). The ouabainthyroglobulin conjugate was purified by Sephadex G-50 gel filtration.…”

Section: Radioimmunoassaysmentioning

confidence: 99%

Radioimmunoassay of plasma ouabain in healthy and pregnant individuals

Vakkuri

Árnason²,

Pouta³

et al. 2000

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…36 In brief, ouabain-BSA conjugate, subsequently used to immunize rabbits was prepared as described by Masugi et al 37 A total 500 mg of ouabain-BSA in CFA were injected intramuscularly and subcutaneously into 3-to 4-month-old rabbits. The animals were rechallenged as above 7 times at 6-week intervals, with the same amount of antigen emulsified in incomplete Freund's adjuvant.…”

Section: Preparation and Concentration Of Anti-ouabain Antibodymentioning

confidence: 99%

Reduction in Maternal Circulating Ouabain Impairs Offspring Growth and Kidney Development

Dvela‐Levitt¹,

Ami²,

Rosen³

et al. 2015

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Ouabain, a steroid present in the circulation and in various tissues, was shown to affect the growth and viability of various cells in culture. To test for the possible influence of this steroid on growth and viability in vivo, we investigated the involvement of maternal circulating ouabain in the regulation of fetal growth and organ development. We show that intraperitoneal administration of anti-ouabain antibodies to pregnant mice resulted in a .80% decline in the circulating ouabain level. This reduction caused a significant decrease in offspring body weight, accompanied by enlargement of the offspring heart and inhibition of kidney and liver growth. Kidney growth inhibition was manifested by a decrease in the size and number of nephrons. After the reduction in maternal circulating ouabain, kidney expression of cyclin D1 was reduced and the expression of the a1 isoform of the Na + , K + -ATPase was increased. In addition, the elevation of proliferation signals including ERK1/2, p-90RSK, Akt, PCNA, and Ki-67, and a reduction in apoptotic factors such as Bax, caspase-3, and TUNEL were detected. During human pregnancy, the circulating maternal ouabain level increased and the highest concentration of the steroid was found in the placenta. Furthermore, circulating ouabain levels in women with small-for-gestational age neonates were significantly lower than the levels in women with normal-for-gestational age newborns. These results support the notion that ouabain is a growth factor and suggest that a reduction in the concentration of this hormone during pregnancy may increase the risk of impaired growth and kidney development.

show abstract

“…Elevated levels of ouabainlike immunoreactivity have been found in patients with primary aldosteronism and essential hypertension. 24 These findings suggest that ouabain or a closely related compound probably has a role in hypertension.…”

Section: Discussionmentioning

confidence: 97%

Chronic blood pressure effects of bufalin, a sodium-potassium ATPase inhibitor, in rats.

Pamnani

Chen²,

Yuan³

et al. 1994

Hypertension

View full text Add to dashboard Cite

Endogenous Na + ,K + -ATPase inhibitors may have a role in the mechanism of low-renin hypertension. Two such compounds have been characterized: ouabain from human plasma and resibufogenin from toad plasma. Previously, we examined the acute effects of ouabain and bufalin (which has the same structure as resibufogenin except for one H + ) in normal rats. Bufalin raised blood pressure, but ouabain had little effect. In contrast, given chronically, ouabain substantially increased blood pressure in normal rats and 70% reduced renal mass rats on a salt-free diet. We have now examined the chronic effects of bufalin in rats. Normal rats received 14.8 ng/kg per day bufalin or an equimolar dose of ouabain intraperitoneally for 6 weeks; 70% reduced renal mass rats also received 14.8 fig/kg per day bufalin. Another group of normal rats received 29.6 jig/kg per day bufalin intraperitoneally for 6 weeks. Respective control animals received vehicle.In contrast to ouabain, blood pressure did not increase in normal rats receiving the 14.8 ^tg dose of bufalin. However, normal rats receiving 29.6 /ig bufalin and 70% reduced renal mass rats receiving 14.8 fig bufalin developed significant increases in blood pressure. Increases in blood pressure were associated with decreases in myocardial Na + ,K + -ATPase activity and correlated with increased plasma Na + ,K + -ATPase inhibitory activity. Thus, although bufalin is a more potent pressor agent than ouabain when both agents are given acutely, ouabain is at least as potent a vasopressor agent as bufalin when given chronically. Thus, both are pressor agents, more so in the presence of reduced renal mass, when given chronically in the rat. 13 Numerous investigators have attempted to isolate this endogenous NKA inhibitor. However, only two steroid NKA inhibitors have been purified and chemically characterized -resibufogenin, a bufodienolide derivative in toad skin and plasma, 14 and a substance with the same basic structure as ouabain from human plasma. 15 In an earlier study 16 designed to determine whether such endogenous inhibitors in fact produce the above cardiovascular changes, we compared the acute effects of equimolar doses of commercially available bufalin (aglycone, identical to resibufogenin except for one H + ) and ouabain (Fig 1) in normal rats. Bufalin infused intravenously into anesthetized rats increased BP, dP/dt, heart rate, urine volume, and urinary sodium excretion. When applied to tail arteries from normal rats in vitro, bufalin depolarized vascular smooth muscle cell membrane potentials. Although equimolar doses of ouabain caused the same directional changes in all parameters except heart rate and membrane potentials, the magnitudes of these changes were always less than those produced by bufalin (ouabain had no effect on heart rate or vascular smooth muscle cell membrane potentials). In fact, ouabain actually decreased BP at higher doses. In contrast, in a subsequent study 17 we found that ouabain given chronically raised BP in both normal and 70% reduced ...

show abstract

Circulating factor with ouabain-like immunoreactivity in patients with primary aldosteronism

Cited by 51 publications

References 10 publications

Radioimmunoassay of plasma ouabain in healthy and pregnant individuals

Radioimmunoassay of plasma ouabain in healthy and pregnant individuals

Reduction in Maternal Circulating Ouabain Impairs Offspring Growth and Kidney Development

Chronic blood pressure effects of bufalin, a sodium-potassium ATPase inhibitor, in rats.

Contact Info

Product

Resources

About