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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro metabolism of progesterone and cholesterol by the adrenal glands and hepatic delta 4-reductase activity of SHR and ARH were investigated to clarify the possible hyperactivity of the pituitary-adrenal axis and abnormal steroid metabolism in SHR. The increased conversion rate of progesterone to 11 beta-hydroxyprogesterone, corticosterone and 18-hydroxy-deoxycorticosterone and the increased biosynthesis of pregnenolone from cholesterol were noted in ARH, which were similar to those seen with chronic ACTH administration. On the other hand, adrenal steroidogenesis in SHR showed no difference from that of control. Therefore the apparently normal adrenal steroidogenesis in SHR may suggest that the adrenal gland is not involved in the spontaneous hypertension of rats. The markedly decreased hepatic delta 4-reductase activity in ARH and SHR was observed in this investigation.
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PMID:Adrenal steroidogenesis and hepatic corticosteroid metabolism in hypertensive rats. 66 27

Results of our previous studies revealed a derangement in the peripheral metabolism of adrenal steroids in patients with essential hypertension. To investigate further this finding, all indIVidual free and conjugated metabolites of cortisol were isolated, identified and quantitated in plasma of 14 normotensive subjects and 13 patients with benign, uncomplicated essential hypertension, following iv administration of a tracer dose of [4-14-C] cortisol. In addition, plasma levels of endogenous cortisol were determined at 8 AM and 4 PM in all the subjects examined. The results obtained revealed the following statistically significant differences between normotensives and hypertensives: 1) Mean plasma concentrations of cortisol metabolites reduced in ring-A with nonreduced 20-ketone, tetrahydrocortisol, tetrahydrocortisone, and their 5alpha-epimers, were 30% lower in the hypertensives; since these steroids constitute the bulk of the major group of cortisol metabolites--the glucuronide conjugates, plasma levels of this group of conjugates measured in toto were also found to be significantly lower in the hypertensives. 2) Concentrations of cortisol metabolites with non-reduced ring-A (delta-4-3-keto configuration preserved) but with reduced 20-ketone and/or hydroxylated at C-6, 20alpha- and 20beta- dihydrocortisol, 6alpha- and 6beta-hydroxycortisol, and 6-hydroxy-20-dihydrocortisol (all 4 isomers), were 73%, 48% and 68% respectively, higher in the hypertensives; since these steroids constitute the bulk of the sulfate-conjugated and nucleoside-complexed metabolites of cortisol, plasma levels of these groups of metabolites, measured in toto, were also found to be higher in the hypertensives. No significant difference was found between normotensives and hypertensives in the AM and PM plasma levels of cortisol. These findings, in conjunction with the results of our studies on urinary corticosteroid metabolites, which yielded identical findings, provide evidence for a decreased activity of hepatic cortisol-delta-4-hydrogenase enzyme system and increased activities (presumably compensatorily) of cortisol-20-reductase and 6-hydroxylase enzyme systems in patients with essential hypertension. The interrelation of these findings with those of other investigators studying steroid metabolites in hypertension, points to the corticosteroid metabolizing enzymes may be an etiological factor in essential hypertension.
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PMID:Corticosteroids in human blood. VIII. Cortisol metabolites in plasma of normotensive subjects and patients with essential hypertension. 113 61

Ingestion of licorice or treatment with chemical derivatives of glycyrrhetinic acid (GA), an active principle of licorice, can cause hypertension, sodium retention, and hypokalemia. Although GA has been shown to inhibit 11 beta-hydroxysteroid dehydrogenase, it may not be the only hepatic enzyme affected by this licorice derivative. Therefore, we studied the effects of GA on other major hepatic steroid-metabolizing enzymes from adrenalectomized male rats using aldosterone as the substrate; namely, delta 4-5 alpha- and delta 4-5 beta-reductases and 3 alpha- and 3 beta-hydroxysteroid dehydrogenases (3 alpha- and 3 beta-HSD). From these in vitro studies, we demonstrated that GA does not affect either microsomal 5 alpha-reductase or cytosolic 3 alpha-HSD activity. However, GA is a potent inhibitor of cytosolic 5 beta-reductase; the K(is) and K(ii) were calculated from enzyme kinetic analysis to be 6.79 and 5.41 microM, respectively, using the Cleland equation, indicating that GA is a noncompetitive inhibitor of aldosterone. In addition, GA specifically inhibited microsomal 3 beta-HSD enzyme activity by what appears to be a competitive inhibition mechanism, causing a build-up of the intermediate, 5 alpha-dihydroaldosterone (DHAldo). Thus, this study has indicated that GA has a profound effect on hepatic ring A-reduction of aldosterone. Inhibition of 5 beta-reductase and 3 beta-HSD results in decreased synthesis of both 3 alpha, 5 beta-tetrahydroaldosterone (THAldo) and 3 beta, 5 alpha-THAldo and, hence, accumulation of aldosterone and 5 alpha-DHAldo, both potent mineralocorticoids.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of the licorice derivative, glycyrrhetinic acid, on hepatic 3 alpha- and 3 beta-hydroxysteroid dehydrogenases and 5 alpha- and 5 beta-reductase pathways of metabolism of aldosterone in male rats. 232 27

The practicability and tolerability of trilostane, a competitive inhibitor of 3 beta-hydroxysteroid-delta 5-dehydrogenase, for the therapy of primary aldosteronism was assessed in 1 patient with aldosterone-producing adenoma (APA) and 3 subjects with idiopathic adrenal hyperplasia (IHA). Trilostane afforded reduction of plasma levels of aldosterone, progesterone, deoxycorticosterone, 17-OH progesterone, cortisol, delta 4-androstenedione, and urinary excretion of 17-hydroxycorticosteroid. Conversely, circulating levels of dehydroepiandrosterone, dehydroepiandrosterone sulfate, and urinary excretion of 17-ketosteroids were increased following this drug therapy. Suppression of mineralo- or glucocorticoid biosynthesis was accompanied by an increase in plasma renin activity. One patient with APA or 3 subjects with IHA showed slight or remarkable improvement of hypertension and hypokalemia. Based on these findings, efficacy and tolerability of trilostane appear to aid in the treatment of IHA.
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PMID:Primary aldosteronism treated by trilostane (3 beta-hydroxysteroid dehydrogenase inhibitor). 298 27

Results of supraphysiological adrenocorticotropic hormone (ACTH) stimulation of biosynthetic pathways of adrenal zona fasciculata indicate that a deficiency of 11-hydroxylase exists in patients with essential hypertension. The deficiency is suggested by the much greater stimulus of synthesis of deoxycorticosterone (DOC) and deoxycortisol in hypertensive subjects than in controls (p less than 0.001). No significant difference in the synthesis of cortisol, corticosterone, progesterone, 17-hydroxyprogesterone (17-OHP), and delta-4-androstenedione (D4) was observed between the two groups. The ratios for synthesis of DOC and corticosterone and for deoxycortisol and cortisol found in hypertensive patients were significantly higher than those found in controls (p less than 0.001); no significant difference was observed in the synthesis of 17-OHP and progesterone. The synthesis of DOC and deoxycortisol was not significantly correlated with either blood pressure or plasma renin activity. Plasma renin activity was significantly lower in hypertensive subjects than in normotensive subjects (p less than 0.0001), while no difference was found in aldosterone secretion between the two groups. The 11-hydroxylase deficiency in the adrenal zona fasciculata may be one of the genetic factors causing hypertension together with environmental factors (particularly salt intake and work-related stress). The investigation performed in our study may be useful for the evaluation of adrenal zona fasciculata enzymatic activities during the study of hypertensive patients.
Hypertension
PMID:Partial deficiency of adrenal 11-hydroxylase. A possible cause of primary hypertension. 298 17

Hormonal measurements in maternal urine and amniotic fluid (AF) during pregnancy and/or at delivery correctly predicted the postnatal diagnosis of 11 beta-hydroxylase deficiency congenital adrenal hyperplasia (11 beta-OH deficiency CAH) in 7 fetuses at risk. In the 4 affected ones, maternal urinary tetrahydro-11-deoxycortisol (THS) excretion was high during the first trimester [0.3-2.2 mg/day (1.1-7.7 mumol/day)] and rose further during the third trimester [0.5-3.5 mg/day (1.8-12.3 mumol/day)] compared to urinary THS excretion in 20 normal pregnancies of the same gestational age (P less than 0.01). In 1 mother, dexamethasone administration (2 mg/day for 72 h) greatly reduced urinary THS excretion (and plasma steroid levels). Urinary THS excretion was low after delivery in these mothers, in normal pregnancies, and in parents of affected individuals [less than 0.05 mg/day (less than 0.08 mumol/day); P = NS]. However, 2 of the 3 heterozygous mothers who carried nonaffected fetuses excreted moderately increased amounts of THS during pregnancy, ranging from 0.15-0.26 mg/day (0.53-0.91 mumol/day), significantly higher than normal (P less than 0.01). Although urinary THS excretion in these mothers was similar to that in 2 mothers with affected fetuses early in pregnancy, urinary THS excretion was higher in mothers with affected compared to those with nonaffected fetuses after the first trimester (P less than 0.01). AF THS and 11-deoxycortisol concentrations were markedly elevated in pregnancies with affected fetuses (P less than 0.01), but normal in nonaffected ones. AF delta 4-androstenedione levels were high in 2 pregnancies and borderline elevated in a third. Although the AF tetrahydrocortisol and tetrahydrocortisone levels were always within the normal range, the AF THS to tetrahydrocortisol plus tetrahydrocortisone ratio was significantly elevated in all pregnancies with affected fetuses (2.8-5.5; P less than 0.01) and normal in nonaffected ones (0.48-1.2; P = NS) compared to that in 160 normal pregnancies [0.64 +/- 0.34 (+/- SD)]. AF 17-hydroxyprogesterone, testosterone, and 11-deoxycorticosterone levels were normal in all pregnancies. Maternal plasma 11-deoxycortisol and delta 4-androstenedione concentrations, determined sequentially throughout gestation, were variable and did not contribute to prenatal diagnosis. All affected infants were born hyperpigmented, 2 were large for gestational age, and the female was severely virilized. In the first week of life 2 males developed severe hypertension with seizures and adrenal insufficiency, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:11 Beta-hydroxylase deficiency congenital adrenal hyperplasia: update of prenatal diagnosis. 334 60

A female newborn infant with ambiguous genitalia was found to have hypertension (121/82 mm Hg) immediately after birth. The plasma testosterone (T) (0.73 nmol/l), delta 4-androstenedione (delta 4-A) (5.9 nmol/l), dehydroepiandrosterone (DHEA) (8.9 nmol/l), as well as 17 OH-hydroxyprogesterone (17 OHP) (152 nmol/l) were elevated. The diagnosis of 11 beta-hydroxylase deficiency was finally established on the basis of elevated plasma eleven-deoxycortisol (compound S) (greater than 0.6 mumol/l) and confirmed by the normalisation of the blood pressure during hydrocortisone therapy. Our case is probably the youngest patient with 11 beta-hydroxylase deficiency in whom the hypertension was found at birth.
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PMID:Hypertension in a neonate with 11 beta-hydroxylase deficiency. 387 97

Four cases in adults of a deficiency in the 11 beta-hydroxylation of corticosteroids were investigated by both basal and dynamic biological studies. Symptoms varied from patient to patient; hirsutism, menstrual disturbance, acne, deepening of the voice, and arterial hypertension appeared post puberty. Basal testing demonstrated elevated levels of plasma androgens. These include delta 4-androstenedione (patients, 3.80-6.43 ng/ml; normal, 1.33 +/- 0.33 ng/ml), urinary 17-ketosteroids (patients, 11.8-16.7 mg/24 h; normal, 5-10 mg/24 h), and urinary dehydroepiandrosterone. The basal tests were often insufficient to show the accumulation of the precursors (especially 17-hydroxyprogesterone) which are often given as evidence for an increase in ACTH stimulation. In studying the levels of the mineralocorticoids, there was shown to be an increased basal level of tetrahydrodeoxycorticosterone (patients, 142-317 microgram/24 h; normal, 60-80 microgram/24 h) which was raised by ACTH stimulation. These results, therefore, confirm the characteristic partial enzyme defect and give evidence for the heterogeneity of this syndrome. Based on the above observations, we believe it is appropriate to rename this condition adult adrenocortical 11 beta-hydroxylation defect rather than late-onset congenital adrenal hyperplasia.
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PMID:Adrenocortical 11 beta-hydroxylation defect in adult women with postmenarchial onset of symptoms. 624 34

Six women aged from 17 to 30 years (mean: 21 years) were referred on account disorders which had begun at puberty and had been present for 3 to 15 years. The reasons for consulting were hirsutism in 5 cases and sterility in one. The patients' height (1.61 to 1.70 m; mean: 1.64 m) and weight (54 to 70 kg; mean: 59 kg) were normal. Three women menstruated regularly and 3 had anovular spaniomenorrhaea. Hirsutism with enlargement of the clitoris (Prader's stage I) was apparent in all six cases. Three patients had permanent, though moderate hypertension. The biochemical changes essential to the diagnosis were as follows: 1) in 2 women with 21-hydroxalyse deficiency there was a rise in cortisol precursors (plasma 17-OH progesterone and its urinary metabolite, pregnanetriol). In 4 women with 11-hydroxylase deficiency urinary 17-OH corticosteroids were increased; two had high desoxycorticol levels. A rise in plasma desoxycortisol/cortisol ration under tetracosactrin stimulation is of considerable diagnostic value; 2) plasma androgens (testosterone, delta 4 androstenedione) and their urinary metabolites (17-ketosteroids) were increased; 3) all abnormalities disappeared when the adrenal function was suppressed. Under dexamethasone treatment hirsutism became stabilized or even regressed, blood pressure values rapidly returned to normal, menstrual disorders disappeared and ovular cycles were established. Three women became pregnant and delivered on term.
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PMID:[Late diagnosis hyperandrogenism due to adrenal enzyme deficiency (author's transl)]. 625 9

To assess the integrated cardiopulmonary response to acute microvascular lung injury, we infused zymosan-activated plasma (ZAP) into mature, awake sheep. ZAP infusion resulted in an immediate increase in the mean pulmonary artery pressure (PAP) from 17.5 +/- 4.5 mm Hg to a maximum of 33.0 +/- 5.4 mm Hg by 5 min (p less than 0.01) of a 90-min infusion. The pulmonary artery hypertension (PAH) was sustained throughout ZAP infusion, and for up to 30 min after infusion was completed (p less than 0.05). Lung lymph flow increased immediately, but lymph to plasma total protein ([L/P]) ratios remained unchanged, suggesting increased pulmonary microvascular permeability. The PaO2 fell to a minimum by 5 min (106.9 +/- 17 to 88.3 +/- 14 mm Hg; p less than 0.01), but recovered toward preinfusion values in the final 60 minutes of ZAP infusion. The cardiac index (CI) and stroke volume index (SVI) also fell significantly for 15 minutes (p less than 0.01), and then recovered to levels not different from baseline by 30 min. In parallel with all of these changes, the polymorphonuclear leukocyte count (PMN) in arterial blood fell immediately [baseline to 5 min, delta 4.9 +/- 2.5 (X 10(3))/mm3; (p less than 0.01)] due to sequestration within the pulmonary microvasculature, since a baseline PMNs were being released from the lung, -6.0 +/- 19%, while by 15 min the PMNs were being sequestered, +58.4 +/- 31% (p less than 0.01). Therefore, ZAP infusion reproduced the clinical picture of acute microvascular lung injury in humans, specifically acute PAH and increased pulmonary microvascular permeability. These two changes were due to a cascade of events associated with the pulmonary microvascular trapping of PMNs.
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PMID:The effect of an infusion of zymosan-activated plasma on hemodynamic and pulmonary function in sheep. 670 53


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