19-hydroxy-4-androstene-3-17-dione and Hypertension

Topics: Androstenedione; Animals; Desoxycorticosterone; Humans; Hypertension

Topics: Aldosterone; Androstenedione; Animals; Desoxycorticosterone; Female; Humans; Hypertension; Pregnancy; Rats

The present study was performed to clarify changes in plasma levels of 19-hydroxyandrostenedione (19-OH-AD), an amplifier of aldosterone and a possible hypertensinogenic steroid, during several tests for the renin-angiotensin system in 20 patients with aldosterone-producing adenoma (APA) and to determine whether 19-OH-AD participates in the etiology of the hypertension in this disorder. Basal plasma 19-OH-AD levels in patients with APA were significantly lower than those in 50 normal subjects, and correlated positively with basal plasma cortisol levels (r = 0.45, P < 0.05). Plasma 19-OH-AD levels were not changed significantly by 2-h standing during which plasma renin activity (PRA) remained suppressed. With 40 mg iv furosemide plus 2-h standing during which PRA remained suppressed, plasma 19-OH-AD levels increased significantly with a concomitant significant increase in plasma cortisol. With dexamethasone pretreatment, however, such positive responses of plasma 19-OH-AD and cortisol disappeared. After the removal of the APA with the adjacent adrenal tissue, PRA and plasma aldosterone concentrations became normal or low-normal, but plasma 19-OH-AD and cortisol did not change as compared with the preoperative levels. There were no significant correlations between basal plasma 19-OH-AD levels and mean blood pressure either before or after the adrenal operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenoma; Adrenal Gland Neoplasms; Adult; Aged; Aldosterone; Androstenedione; Blood Pressure; Dexamethasone; Female; Furosemide; Humans; Hypertension; Male; Middle Aged; Radioimmunoassay

We have reported that 19-hydroxyandrostenedione (19-OH-A-dione) amplifies the sodium-retaining action of aldosterone. To evaluate whether it also amplifies the hypertensive action of small doses of aldosterone, mononephrectomized rats were given 0.5 mg aldosterone, 10 mg 19-OH-A-dione or a combination of both once a week for 19 weeks, and changes in blood pressure were evaluated. Rats were given 154 mmol NaCl/l to drink. The blood pressure of controls, rats given aldosterone alone, 19-OH-A-dione alone or a combination of both in week 19 were 137 +/- 4 (S.E.M.), 146 +/- 7, 147 +/- 4 and 191 +/- 8 mmHg respectively. The blood pressure of rats given the combination was significantly higher than any of the other three groups. These results indicate that 19-OH-A-dione amplifies the hypertensive action of aldosterone and may be considered a potent hypertensive agent in the presence of aldosterone. To evaluate whether 19-OH-A-dione amplifies the hypertensive action of small doses of deoxycorticosterone acetate (DOCA), another experiment was carried out in which similar rats were given 5 mg DOCA or a combination of 5 mg DOCA and 10 mg 19-OH-A-dione once a week for 8 weeks. The blood pressure of controls, rats given DOCA alone and a combination of DOCA and 19-OH-A-dione in week 8 were 139 +/- 5, 166 +/- 7 and 208 +/- 12 mmHg respectively. The blood pressure of rats given a combination of DOCA and 19-OH-A-dione was significantly higher than that of control rats or the rats given DOCA alone. These results indicate that 19-OH-A-dione can also amplify the hypertensive action of DOCA. It is concluded that 19-OH-A-dione amplifies the hypertensive action of mineralocorticoids as well as the sodium-retaining action of aldosterone.

Topics: Aldosterone; Androstenedione; Animals; Blood Pressure; Desoxycorticosterone; Dose-Response Relationship, Drug; Drug Synergism; Hypertension; Male; Mineralocorticoids; Rats; Rats, Sprague-Dawley

We have reported that 19-hydroxyandrostenedione (19-OH-A-dione) functions as an amplifier of the sodium-retaining and hypertensive action of aldosterone. We therefore measured 19-hydroxyandrostenedione in hypertensive patients.. We studied 53 normal male control subjects and 63 male patients with essential hypertension (48 patients with normal renin essential hypertension and 15 patients with high renin essential hypertension). Plasma 19-OH-A-dione levels were measured by RIA.. Plasma 19-OH-A-dione concentrations in control subjects and patients with normal and high renin essential hypertension were 115 +/- 46 (mean +/- SD), 112 +/- 49 and 201 +/- 79 pmol/l, respectively. Patients with high renin essential hypertension showed significantly higher 19-OH-A-dione concentrations than did control subjects. The evaluation of the correlation between plasma 19-OH-A-dione concentrations and plasma renin activity revealed that plasma 19-OH-A-dione concentrations in hypertensive subjects rose gradually with an increase in plasma renin activity. Therefore, a significant correlation was found between plasma renin activity and plasma 19-OH-A-dione (r = 0.586, P < 0.001). In contrast, in control subjects, no significant correlation was found between plasma renin activity and plasma 19-OH-A-dione (r = 0.059, P > 0.05).. The secretion of 19-OH-A-dione from the adrenal cortex is under the control of the renin-angiotensin system in hypertensives but not in normotensives.

Topics: Adult; Androstenedione; Humans; Hypertension; Male; Middle Aged; Radioimmunoassay; Renin

19-hydroxy-androstenedione (19-OH-A), a C19 steroid, is an amplifier of the sodium retaining action of aldosterone under the control of ACTH and renin-angiotensin system. These findings suggest that 19-OH-A may be involved in the regulation of hydroelectrolyte balance and blood pressure. Aim of the present study was to examine the behaviour of 19-OH-A in normal volunteers (N) and in patients with Essential Hypertension (EH) in basal conditions and after dynamic tests such as postural changes, physical exercise and ACTH administration. The significant increase in 19-OH-A after ACTH confirms its adrenal origin. During bicycle exercise the significant increase in plasma catecholamines, renin-activity, aldosterone, blood pressure and heart rate at maximum effort was not associated with a parallel increase in 19-OH-A. No significant differences were found in plasma 19-OH-A levels between N and EH patients both in basal conditions and after dynamic tests. Therefore, our findings seem to exclude an important role of 19-OH-A in the pathogenesis of EH.

Topics: Adrenocorticotropic Hormone; Adult; Aldosterone; Androstenedione; Catecholamines; Exercise Test; Humans; Hypertension; Middle Aged; Renin; Supine Position

Topics: 17-alpha-Hydroxyprogesterone; 18-Hydroxydesoxycorticosterone; Adrenal Hyperplasia, Congenital; Androstenedione; Blood Pressure; Cushing Syndrome; Humans; Hydroxyprogesterones; Hyperaldosteronism; Hypertension

Because of the association of preeclampsia with hydatidiform mole, and since levels of 19-hydroxyandrostenedione (19-OH-A) and androstenedione (A) are raised in hypertensive diseases of pregnancy, we compared plasma 19-OH-A and A in hydatidiform mole patients with control early pregnant women. Both steroids were significantly elevated in 27 patients with partial or complete hydatidiform moles, as compared with the levels in 36 control pregnancies at similar stages of gestation.

Topics: Androstenedione; Female; Humans; Hydatidiform Mole; Hypertension; Pregnancy; Pregnancy Complications, Cardiovascular; Uterine Neoplasms

To study the serum levels of 19-hydroxyandrostenedione (19-OH-A), known as an obligatory intermediate of estrogen biosynthesis and considered to be one of the hypertensinogens, a method using GC-MS with application of synthesized [7,7-d2]androstenedione (A), [7,7-d2] 19-OH-A and [9,11-d2]estrone(E1) as internal standards was newly developed. Normal pregnant women and pregnant women complicated with hypertension near term were selected for the study. The levels of 19-OH-A and E1 increased significantly as gestation progressed [19-OH-A; 224.7 +/- 72.1 (1st trimester), 655.5 +/- 325.4 (2nd trimester). 1517.8 +/- 543.6 (3rd trimester)pg/ml], and a positive correlation was found between the levels of the two steroids. No apparent change was observed in A levels during the course of pregnancy. The mean levels of 19-OH-A in pregnancy complicated with hypertension at 2nd and 3rd trimester were 761.7 +/- 348.9 and 1473.0 +/- 491.4 pg/ml, which were compatible with those in normal pregnancy. The levels of 19-OH-A at delivery in maternal vein (MV) were 1735.1 +/- 683.9 pg/ml. Significantly higher levels of 19-OH-A were found in umbilical vein (UV) (1977.2 +/- 564.9 pg/ml) than those in umbilical artery (109.7 +/- 49.1 pg/ml). 19-OH-A concentration in term placental tissue was 16.3 ng/g.w.w. tissue. This is the first report to demonstrate the serum 19-OH-A levels measured by GC-MS and also to demonstrate the levels in the cord blood. The results indicate that 19-OH-A may be the product of pregnancy and may be derived from the feto-placental compartment.

Topics: Androstenedione; Chemical Phenomena; Chemistry; Estrone; Female; Fetal Blood; Gas Chromatography-Mass Spectrometry; Humans; Hypertension; Labor, Obstetric; Placenta; Pregnancy; Pregnancy Complications, Cardiovascular

Recently, it has been recognized that 19-hydroxyandrostenedione (19-OH-AD), one of the C19 steroids, acts to amplify the mineralocorticoid activity and to elevate blood pressure. However, there is no detailed report about the pressor mechanism and the effects on several humoral depressor factors, i.e., kallikrein, kinin and prostaglandins etc. Therefore, we studied the differences in the pressor mechanisms and the changes in urinary prostaglandin E (PGE) and kinin excretions among deoxycorticosterone acetate (DOCA)-salt hypertension, 19-OH-AD induced hypertension, and testosterone induced hypertension. In this study, DOCA, 19-OH-AD and testosterone were administered subcutaneously to castrated male rats (Wistar rats, 12 weeks) at a dose of 10 mg/body/week for the first 6 weeks. Then the doses were increased to 30 mg/body/week for the next 5 weeks. These experiments were done in metabolic cages. It was found that 19-OH-AD induced hypertension earlier than DOCA and testosterone. However, 19-OH-AD and testosterone had no effect on the levels of urinary kinin and PGE excretions, while DOCA significantly increased urinary kinin and PGE excretions immediately after the onset of hypertension. Furthermore, DOCA increased the urinary Na/K ratio, while 19-OH-AD and testosterone did not change the ratio. It is suggested that 19-OH-AD might induce the pressor action due to the changes in the vascular reactivity rather than the mineralocorticoid activity.

Topics: Androstenedione; Animals; Blood Pressure; Body Weight; Castration; Desoxycorticosterone; Drinking; Hypertension; Kinins; Male; Potassium; Prostaglandins E; Rats; Rats, Inbred Strains; Sodium; Sodium Chloride; Testosterone

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.

Topics: Aldosterone; Androstenedione; Angiotensinogen; Angiotensins; Animals; Corticosterone; Hypertension; Male; Potassium; Rats; Rats, Inbred Strains; Renin; Sodium

Topics: Addison Disease; Adrenocorticotropic Hormone; Aldosterone; Androstenedione; Cushing Syndrome; Female; Furosemide; Humans; Hypertension; Male

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.

Topics: Aldosterone; Androstenedione; Animals; Blood Pressure; Corticosterone; Desoxycorticosterone; Hypertension; Male; Potassium; Rats; Renin