Action of compounds with effective in vivo mineralocorticoid activity on ion transport in leucocytes.

Baron, D N; Green, RJ

doi:10.1111/j.1365-2125.1986.tb02819.x

Cited by 8 publications

(3 citation statements)

References 25 publications

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“…Although CBX produces a marked increase in rectal transmucosal electrical potential difference [25] (an index of mineralocorticoid activity on the rectum), there is no gastrointestinal potassium loss to account for the hypokalaemia [26]. More recently CBX has been shown to stimulate cellular Na+/ K+-adenosine triphosphatase [27] and it is suggested that the hypokalaemia is simply a 'redistribution hypokalaemia' with no nett change in total body potassium.…”

Section: Discussionmentioning

confidence: 99%

Mineralocorticoid activity of carbenoxolone: contrasting effects of carbenoxolone and liquorice on 11β-hydroxysteroid dehydrogenase activity in man

Stewart¹,

et al. 1990

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1. 11-beta-Hydroxysteroid dehydrogenase is an enzyme complex consisting of 11 beta-dehydrogenase and 11-oxoreductase responsible for the interconversion of cortisol to cortisone in man. Inhibition of 11 beta-dehydrogenase (e.g. after liquorice ingestion) results in cortisol acting as a potent mineralocorticoid. We have evaluated the effect of the synthetic liquorice derivative, carbenoxolone, on this enzyme complex. 2. Carbenoxolone given to six volunteers in metabolic balance produced sodium retention with suppression of the renin-angiotensin-aldosterone system. Plasma potassium fell, although there was no kaliuresis. This was associated with inhibition of 11 beta-dehydrogenase (as measured by a rise in the plasma half-life of [11 alpha-3H]cortisol). Unlike liquorice, however, carbenoxolone also inhibited 11-oxoreductase (as measured by the generation of cortisol after oral cortisone acetate). 3. The mineralocorticoid activity of carbenoxolone, like liquorice, is mediated via cortisol by inhibition of 11 beta-dehydrogenase. Carbenoxolone, however, also inhibits 11-oxoreductase activity and this may relate to its effect on renal potassium excretion.

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Section: Discussionmentioning

confidence: 99%

Mineralocorticoid activity of carbenoxolone: contrasting effects of carbenoxolone and liquorice on 11β-hydroxysteroid dehydrogenase activity in man

Stewart¹,

et al. 1990

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“…Cx has been found to have effects on ion transport in leukocytes that are independent of those of either mineralocorticoids or glucocorticoids. 36 Placental regulation of the ionic content of amniotic fluid, particularly of sodium and potassium, has been implicated in blood pressure programming in SHR 37 and might be important in genetically normotensive animals.…”

Section: Discussionmentioning

confidence: 99%

Maternal Hypertension and Progeny Blood Pressure

Gómez-Sánchez

1999

Hypertension

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Abstract-Epidemiological and experimental evidence suggests that gestational events modulate the level of blood pressure that will be "normal" for the individual as an adult. Glucocorticoid excess during gestation is associated with low birth weight, a large placenta, and adult hypertension in humans and animals. It has been proposed that the deficiency in placental 11␤-hydroxysteroid dehydrogenase activity in humans produces a gestational hormonal milieu, notwithstanding normal circulating levels of glucocorticoids, that predisposes the adult progeny to hypertension. Animal studies indicate that maternal hypertension, excess glucocorticoids, and hydroxysteroid dehydrogenase inhibition program adult blood pressure. Blood pressures of Sprague-Dawley rat dams were manipulated during gestation with continuous intracerebroventricular infusions of vehicle, aldosterone, 11␣-hydroxyprogesterone, or carbenoxolone at doses known to produce hypertension with no renal effects or with subcutaneous infusions of larger, equally hypertensinogenic doses that produce systemic effects. Blood pressures of all treated dams were significantly greater (PϽ0.01) during gestation than those of the vehicle ICV control rats but not significantly different from each other. The blood pressures of both male and female progeny (nՆ6 per group, comprising representatives from at least 4 litters) were measured after 6 weeks of age. No significant difference was found in the blood pressure of the pups regardless of the maternal gestational blood pressure or treatment with an enzyme inhibitor, even after high-salt diet challenge. Key Words: hypertension, essential Ⅲ aldosterone Ⅲ mineralocorticoids Ⅲ glucocorticoids Ⅲ 11␤-hydroxysteroid dehydrogenase Ⅲ gestation Ⅲ carbenoxolone Ⅲ 11␣-hydroxyprogesterone T he multiple interacting causes of essential hypertension may be classified as genetic or environmental (which includes the fetal milieu). The combination of low term birth weight and large placenta, an indicator of an adverse fetal environment, is associated with malnutrition, hypoxia, severe maternal anemia, decreased blood flow to the fetus, and glucocorticoid excess. 1 Low term birth weight has been reported to be a significant risk factor for cardiovascular disease, which includes hypertension, later in life. 1-3 A review of published epidemiological studies found reports in which no association between term birth weight and adult blood pressure was indicated as well as studies in which a negative correlation existed, but high term birth weight was not found to be correlated with hypertension in the adult. Birth weight correlated positively with neonatal blood pressure but did not consistently predict adolescent blood pressure. 4 A prospective study of black Americans found that term birth weight did not correlate with adult blood pressure, although blood pressure and weight at 4 months of age did predict subsequent blood pressures through age 28 years. 5 The 11␤-hydroxysteroid dehydrogenase (11␤-HSD) enzyme family comprises at least 2 isofor...

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“…In contrast, in rats, carbenoxolone has been shown to produce a kaliuresis (Souness & Morns, 1989) and in uitro had no effect on the conversion of 1 I-dehydrocorticosterone to corticosterone at concentrations which markedly inhibit the dehydrogenase reaction . Possible explanations for these differences may be provided by the observations that in rats carbenoxolone potentiated the actions of other natural and synthetic corticosteroids which do not have an 1 1-hydroxyl group and therefore are not metabolized by 11B-OHSD (Morris & Souness, 1990;Funder et al, 1990), and had direct effects on membrane electrolyte transport independent of the presence of corticosteroids (Baron & Green, 1986).…”

Section: Cllnical Significance Of 11p-ohsdmentioning

confidence: 99%

11β‐Hydroxysteroid dehydrogenase and enzyme‐mediated receptor protection: Life after liquorice?

Walker

Edwards

1991

Clinical Endocrinology

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Plasma renin activity was undetectable and mineralocorticoid excess was suspected. However, plasma aldosterone was low and ?no other mineralocorticoids could be identified. Cortisol metabolites as measured by urinary 17-hydroxycorticosteroids were low as was urinary tetrahydrocortisone (THE). After ACTH it was noted that 'surprisingly THE remained low'. The significance of this was not understood and it was speculated that an unknown steroid with both P-OHSD deficiencyIn 1974 Werder (Werder et al., 1974) described a case of a 3year-old girl with severe hypertension and hypokalaemia.prolongation of the half life of (1 1 cr3H)-F (which is acted on by 1 1 /3-OHSD to produce 3H-H20 and unlabelled cortisone);

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Action of compounds with effective in vivo mineralocorticoid activity on ion transport in leucocytes.

Cited by 8 publications

References 25 publications

Mineralocorticoid activity of carbenoxolone: contrasting effects of carbenoxolone and liquorice on 11β-hydroxysteroid dehydrogenase activity in man

Mineralocorticoid activity of carbenoxolone: contrasting effects of carbenoxolone and liquorice on 11β-hydroxysteroid dehydrogenase activity in man

Maternal Hypertension and Progeny Blood Pressure

11β‐Hydroxysteroid dehydrogenase and enzyme‐mediated receptor protection: Life after liquorice?

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