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Biomedical subjects

H Sekihara

Publications and source records attributed to H Sekihara.

At least 109 records · Page 6Linked to original sources
PubMed1987

Enhancement of the hypertensinogenic action of 19-hydroxyandrostenedione by aromatase inhibitor, delta 1-testololactone.

To evaluate the enhancing effects of 1,2-dehydrotestololactone (delta 1-testololactone) on the hypertensinogenic action of 19-hydroxyandrostenedione (19-OH-A-dione), 1 mg 19-OH-A-dione, 10 mg delta 1-testololactone, or a combination of 1 mg 19-OH-A-dione and 10 mg delta 1-testololactone was injected into intact rats drinking water once a week for 4 weeks. The blood pressure of control rats and rats given 19-OH-A-dione, delta 1-testololactone, and a combination of 19-OH-A-dione and delta 1-testololactone in the fourth week was 130 +/- 2 (SE), 140 +/- 2, 128 +/- 6, and 152 +/- 5 mmHg, respectively. The blood pressure of rats given 19-OH-A-dione and a combination of 19-OH-A-dione and delta 1-testololactone was significantly higher than that of control rats. In addition, the blood pressure of rats given a combination of 19-OH-A-dione and delta 1-testololactone was significantly higher than that of rats given 19-OH-A-dione alone. As delta 1-testololactone itself did not show any hypertensinogenic action, it is considered to enhance the hypertensinogenic action of 19-OH-A-dione. Although plasma 19-OH-A-dione concentrations of control rats and rats given delta 1-testololactone were lower than the sensitivity of RIA, those of rats given 19-OH-A-dione and a combination of 19-OH-A-dione and delta 1-testololactone were 116 +/- 3 and 222 +/- 37 pg/ml, respectively. Plasma 19-OH-A-dione concentrations of rats given a combination of 19-OH-A-dione and delta 1-testololactone were significantly higher than those of rats given 19-OH-A-dione alone. Therefore, delta 1-testololactone is considered to enhance the action of 19-OH-A-dione by increasing plasma concentrations of 19-OH-A-dione. As delta 1-testololactone is an aromatase inhibitor, the inhibition of the conversion of circulating 19-OH-A-dione to estrogens in peripheral tissues might be the cause of the elevation of plasma 19-OH-A-dione concentrations. These results indicate that aromatose inhibitors enhance the hypertensinogenic action of 19-OH-A-dione by decreasing the degradation of 19-OH-A-dione.

Androstenedione↗
PubMed1986

Plasma levels of atrial natriuretic peptide in primary aldosteronism and essential hypertension.

Plasma levels of atrial natriuretic peptide (ANP) were measured in 9 patients with primary aldosteronism and 41 patients with essential hypertension (class I or II by WHO classification) using a specific and sensitive RIA. The mean plasma ANP concentration in patients with primary aldosteronism (mean +/- SEM, 67.1 +/- 10.8 pg/ml; n = 9) was significantly higher than that in healthy normotensive subjects (37.9 +/- 1.4 pg/ml; n = 108) or patients with essential hypertension (38.5 +/- 2.8 pg/ml; n = 41). During treatment with spironolactone, plasma levels of ANP declined in 6 of the 7 patients with primary aldosteronism, but no change occurred in the remaining patient who had cardiac enlargement of unknown etiology. The mean plasma ANP concentration in patients with essential hypertension, on the other hand, was not significantly different from that in normal subjects. These results indicate that plasma ANP levels are elevated in patients with primary aldosteronism, probably due to volume expansion, whereas no abnormality in ANP secretion exists in patients with uncomplicated essential hypertension.

Adult↗
PubMed1985

Angiotensin II induces the release of 19-hydroxyandrostenedione in man.

Plasma concentrations of 19-hydroxyandrostenedione [19-hydroxy-4-androstene-3,17-dione (19-OH-A-dione)], which we reported to be an amplifier of the action of aldosterone on the basis of results obtained in bioassays using adrenalectomized rats, were measured in man using a specific and sensitive RIA. Plasma 19-OH-A-dione concentrations (mean +/- SE) in normal subjects were 56 +/- 4 pg/ml in men and 51 +/- 4 pg/ml in women. Plasma 19-OH-A-dione rose significantly during ACTH stimulation and declined significantly during dexamethasone suppression. Plasma 19-OH-A-dione levels in the adrenal vein were an order of magnitude higher than those in the inferior vena cava. These results demonstrate that 19-OH-A-dione is directly secreted by the adrenal cortex and that its secretion is under the control of ACTH. As the action of 19-OH-A-dione may be closely related to that of aldosterone, the response of 19-OH-A-dione to angiotensin II infusion was evaluated and compared with that of aldosterone. During the infusion of graded doses (0.5-4.0 ng/kg . min) of angiotensin II, plasma 19-OH-A-dione increased significantly after the infusion of angiotension II at rates of 1.0 and 2.0 ng/kg . min. It then declined after the infusion of angiotensin II at a rate of 4.0 ng/kg . min. In contrast, plasma aldosterone did not increase significantly until the infusion rate reached 4.0 ng/kg . min. These results indicate that the secretion of 19-OH-A-dione is under the control of angiotensin II. Similar changes in 19-OH-A-dione and aldosterone were found during postural changes. In those subjects who had a small increase in plasma aldosterone when they were upright, 19-OH-A-dione significantly increased. In contrast, in those subjects who had a large increase in plasma aldosterone when upright, 19-OH-A-dione significantly declined. These results suggest that a small elevation of endogenous angiotensin II induces an elevation of plasma 19-OH-A-dione, and a sharp increase in endogenous angiotensin II induces an increase in plasma aldosterone and a decline in plasma 19-OH-A-dione. As angiotensin II stimulated the release of 19-OH-A-dione when the secretion of ACTH was suppressed, angiotensin II acted directly on the adrenal cortex. 19-OH-A-dione is a newly recognized biologically active adrenal C19 steroid which is regulated by both ACTH and the renin-angiotensin system in man.

Adrenocorticotropic Hormone↗
PubMed1984

19-hydroxyandrostenedione and 6 beta-hydroxyandrostenedione: new steroids regulated by the renin-angiotensin system in man.

The changes of plasma 19-hydroxyandrostenedione (19-OH-A-dione) and 6 beta-hydroxyandrostenedione (6 beta-OH-A-dione) during the infusion of angiotensin II were evaluated and were compared with those of plasma aldosterone in man. Angiotensin II was infused into 5 normal subjects with an infusion pump at rates of 0.5, 1.0, 2.0 and 4.0 ng/kg per min. Each dose was infused for 20 min. Plasma 19-OH-A-dione rose significantly following the infusion of angiotensin II at a rate of 0.5 ng/kg per min and plasma 6 beta-OH-A-dione rose significantly following the infusion of angiotensin II at a rate of 1.0 ng/kg per min. In contrast, plasma aldosterone did not change significantly until the infusion rate reached 4.0 ng/kg per min. These results indicate that the secretion of 19-OH-A-dione and 6 beta-OH-A-dione is under the control of angiotensin II and the release of 19-OH-A-dione and 6 beta-OH-A-dione is induced earlier by the smaller doses of angiotensin II prior to the secretion of aldosterone. As 19-OH-A-dione and 6 beta-OH-A-dione amplify the action of aldosterone in bioassays using adrenalectomized rats and work as sodium-retaining and hypertensinogenic agents in intact rats, they are newly recognized biologically active steroids which are regulated by the renin-angiotensin system in man.

Adult↗
PubMed1984

Serum dehydroepiandrosterone sulfate in Cushing's syndrome.

Serum concentrations of dehydroepiandrosterone sulfate (DHEA-S) were measured in patients with hyperadrenocorticism. When compared to normal subjects of corresponding age, serum DHEA-S levels were normal or elevated in 37 patients with Cushing's disease. In contrast, DHEA-S levels were significantly lower than those of normal subjects in all 28 patients with hyperadrenocorticism due to benign adrenocortical adenoma, suggesting that ACTH is the major determinant of DHEA-S secretion and that determination of serum DHEA-S concentrations is useful in the biochemical differential diagnosis of the etiology of Cushing's syndrome. In six patients with adrenocortical adenoma, the recovery of suppressed DHEA-S secretion after removal of the adrenal gland affected by a tumor was studied. Serum cortisol levels normalized by the end of the second year after unilateral adrenalectomy, while DHEA-S levels remained low for at least 2 succeeding yr. The results suggest that deficient ACTH secretion may result in a greater and longer lasting loss in the ability of the adrenal cortex to secrete androgens than in the ability to secrete cortisol.

Adenoma↗
PubMed1983

19-Hydroxyandrostenedione: evidence for a new class of sodium-retaining and hypertensinogenic steroids.

The biological activities of 19-hydroxyandrostenedione (19-OH-A-dione), which we reported as an amplifier of the action of aldosterone on the basis of the results obtained in bioassays using adrenalectomized rats, were evaluated in rats with the adrenals. The administration of 19-OH-A-dione to the rats caused sodium retention, high blood pressure, suppressed PRA and low plasma aldosterone, corticosterone, and deoxycorticosterone concentrations. The sodium-retaining and hypertensinogenic effects of 19-OH-A-dione were more potent than those of deoxycorticosterone acetate. Spironolactone inhibited the action of 19-OH-A-dione. The results indicate that 19-OH-A-dione, although it is devoid of mineralocorticoid activity, works as a potent sodium-retaining agent and causes a hypertensive state simulating mineralocorticoid excess in the presence of the adrenal cortex.

Aldosterone↗
PubMed1983

6 beta-Hydroxyandrostenedione: evidence for a new hypertensinogenic agent.

The hypertensinogenic effects of 6 beta-hydroxyandrostenedione (6 beta-OH-A-dione), which we reported as an amplifier of the kaliuretic action of aldosterone on the basis of the results obtained in bioassays using adrenalectomized rats, were evaluated in rats with the adrenals and compared with those of 19-hydroxyandrostenedione (19-OH-A-dione), an amplifier of the sodium-retaining action of aldosterone. The administration of 6 beta-OH-A-dione to rats with the adrenals caused sodium-retention as the administration of 19-OH-A-dione did and the 6 beta-OH-A-dione treated rats developed high blood pressure, suppressed plasma renin activity and low plasma aldosterone, corticosterone and 11-deoxycorticosterone concentrations as the 19-OH-A-dione treated rats did. The results demonstrate that 6 beta-OH-A-dione works as a hypertensinogenic agent in the presence of the adrenal cortex and causes the hypertensive state simulating mineralocorticoid excess. The present paper adds further evidence for the hypertensinogenic effects of amplifiers of the action of aldosterone and suggests the importance of amplifiers of the action of aldosterone in the etiology of human hypertension.

Aldosterone↗
PubMed1983

19-Hydroxyandrostenedione: a potent hypertensinogenic steroid in man.

The hypertensinogenic effects of 19-hydroxyandrostenedione (19-OH-A-dione), which we reported as an amplifier of the action of aldosterone on the basis of the results obtained in bioassays using adrenalectomized rats, were evaluated in intact rats with both adrenals and kidneys. The administration of 19-OH-A-dione to the rats caused sodium retention and the 19-OH-A-dione treated rats developed high blood pressure, suppressed plasma renin activity and low plasma aldosterone, corticosterone and deoxycorticosterone concentrations. The hypertensinogenic potency of 19-OH-A-dione was incomparably higher than that of DOCA. The results indicate that 19-OH-A-dione is a potent hypertensinogenic steroid and causes the hypertensive state similar to mineralocorticoid excess. The evaluation of 19-OH-A-dione concentrations in human plasma revealed that 19-OH-A-dione is present in human peripheral circulation. It appears to be secreted by the adrenal cortex under the control of ACTH and the renin-angiotensin system. Plasma 19-OH-A-dione concentrations in patients with normal renin essential hypertension and low renin essential hypertension are higher than those in control subjects. 19-OH-A-dione is a newly recognised hypertensinogenic steroid in man.

Adrenocorticotropic Hormone↗
PubMed1982

19-hydroxyandrostenedione as a new hypertensinogenic agent.

The hypertensiogenic effects of 19-hydroxyandrostenedione (19-OH-A-dione) reported previously to be an amplifier of the action of aldosterone were evaluated using the same experimental procedures as for DOCA-salt hypertension in rats. The 19-OH-A-dione treated rats developed high blood pressure, hypokalemia, suppressed plasma renin activity and low plasma aldosterone and corticosterone concentrations as the DOCA treated rats did. The results demonstrate that 19-OH-A-dione amplifies the action of endogenous aldosterone and causes a hypertensive state simulating mineralocorticoid excess. Amplifiers of the action of aldosterone are considered to work as hypertensinogenic agents in the presence of the adrenal cortex.

Aldosterone↗
PubMed1978

New mineralocorticoids: 5alpha-dihydroaldosterone and 5alpha-dihydro-11-deoxycorticosterone.

Mineralocorticoid activity of several delta4-3-ketosteroids and their 5alpha-dihydro analogs were evaluated by bioassay using urinary Na:K ratio of adrenalectomized rats as an index of mineralocorticoid activity. Among delta4-3-ketosteroids, aldosterone, 11-deoxycorticosterone, corticosterone, cortisol, 11-dehydrocorticosterone, and cortisone showed mineralcorticoid activity with aldosterone, the most potent of the series, showing virtually maximum activity at a dose of 0.25 microgram/rat. 5alpha-Dihydroaldosterone and 5alpha-dihydro-11-deoxycorticosterone possessed distinct mineralcorticoid activity, albeit less than aldosterone and 11-deoxycorticosterone. 5alpha-Dihydrocorticosterone, 5alpha-dihydrocortisol, 5alpha-dihydro-11-dehydrocorticosterone, and 5alpha-dihydrocortisone did not show mineralocorticoid activity in doses up to 100 microgram/rat. It is concluded that reduction of the 4.5 double bond diminishes mineralocorticoid activity of delta4-3-ketosteroids. Nevertheless, 5alpha-dihydroaldosterone has distinct mineralocorticoid activity with potency of 1.8% of that of aldosterone and approximately the same as that of 11-deoxycorticosterone.

Aldosterone↗