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Hypertension (Dallas, Tex. : 1979) May 2014
Topics: Animals; Blood Pressure; Cardiovascular Physiological Phenomena; Desoxycorticosterone; Endothelium, Vascular; Humans; Receptors, Mineralocorticoid; Sodium Chloride; Ventricular Remodeling
PubMed: 24566083
DOI: 10.1161/HYPERTENSIONAHA.114.01997 -
Translational Psychiatry Jun 2022There is preliminary evidence that adrenal steroids other than cortisol may be valuable biomarkers for major depressive disorder (MDD). So far, studies have been...
There is preliminary evidence that adrenal steroids other than cortisol may be valuable biomarkers for major depressive disorder (MDD). So far, studies have been conducted in adults only, and conclusions are limited, mainly due to small sample sizes. Therefore, the present study assessed whether adrenal steroids serve as biomarkers for adolescent MDD. In 261 depressed adolescents (170 females) treated at a single psychiatric hospital, serum adrenal steroids (progesterone, 17-hydroxyprogesterone, 21-deoxycortisol, 11-deoxycortisol, cortisol, cortisone, deoxycorticosterone, corticosterone) were determined by liquid chromatography-tandem mass spectrometry. Findings were compared to that of an age- and sex-matched reference cohort (N = 255) by nonparametric analysis of variance. Nonparametric receiver operating characteristics (ROC) analyses were conducted to evaluate the diagnostic performance of single steroids and steroid ratios to classify depression status. Sensitivity analyses considered important confounders of adrenal functioning, and ROC results were verified by cross-validation. Compared to the reference cohort, levels of deoxycorticosterone and 21-deoxycortisol were decreased (P < 0.001). All other glucocorticoid- and mineralocorticoid-related steroids were increased (P < 0.001). The corticosterone to deoxycorticosterone ratio evidenced excellent classification characteristics, especially in females (AUC: 0.957; sensitivity: 0.902; specificity: 0.891). The adrenal steroid metabolome qualifies as a bio-readout reflecting adolescent MDD by a distinct steroid pattern that indicates dysfunction of the hypothalamus-pituitary-adrenal axis. Moreover, the corticosterone to deoxycorticosterone ratio may prospectively qualify to contribute to precision medicine in psychiatry by identifying those patients who might benefit from antiglucocorticoid treatment or those at risk for recurrence when adrenal dysfunction has not resolved.
Topics: Adolescent; Adult; Corticosterone; Depression; Depressive Disorder, Major; Desoxycorticosterone; Female; Humans; Hydrocortisone; Steroids
PubMed: 35717450
DOI: 10.1038/s41398-022-01966-2 -
Metabolism: Clinical and Experimental May 2022High salt intake and aldosterone are both associated with vascular stiffening in humans. However, our preliminary work showed that high dietary salt alone did not...
INTRODUCTION
High salt intake and aldosterone are both associated with vascular stiffening in humans. However, our preliminary work showed that high dietary salt alone did not increase endothelial cell (EC) or vascular stiffness or endothelial sodium channel (EnNaC) activation in mice, presumably because aldosterone production was significantly suppressed as a result of the high salt diet. We thus hypothesized that high salt consumption along with an exogenous mineralocorticoid would substantially increase EC and vascular stiffness via activation of the EnNaC.
METHODS AND RESULTS
Mice were implanted with slow-release DOCA pellets and given salt in their drinking water for 21 days. Mice with either specific deletion of the alpha subunit of EnNaC or treated with a pharmacological inhibitor of mTOR, a downstream signaling molecule involved in mineralocorticoid receptor activation of EnNaC, were studied. DOCA-salt treated control mice had increased blood pressure, EC Na transport activity, EC and arterial stiffness, which were attenuated in both the αEnNaC and mTOR inhibitor treated groups. Further, depletion of αEnNaC prevented DOCA-salt-induced impairment in EC-dependent vascular relaxation.
CONCLUSION
While high salt consumption alone does not cause EC or vascular stiffening, the combination of EC MR activation and high salt causes activation of EnNaC which increases EC and arterial stiffness and impairs vascular relaxation. Underlying mechanisms appear to include mTOR signaling.
Topics: Animals; Blood Pressure; Desoxycorticosterone Acetate; Endothelial Cells; Epithelial Sodium Channels; Hypertension; Mice; Sodium; Vascular Stiffness
PubMed: 35183546
DOI: 10.1016/j.metabol.2022.155165 -
Applied and Environmental Microbiology May 1979Of 37 strains of Eubacterium lentum and phenotypically similar organisms, 26 (70%) synthesized a corticoid 21-dehydroxylase and/or a 3 alpha-hydroxysteroid...
Of 37 strains of Eubacterium lentum and phenotypically similar organisms, 26 (70%) synthesized a corticoid 21-dehydroxylase and/or a 3 alpha-hydroxysteroid dehydrogenase. It appeared that the corticoid 3 alpha-hydroxysteroid dehydrogenase was identical to the bile acid 3 alpha-hydroxysteroid dehydrogenase. Steroid-metabolizing enzymes were found both in E. lentum and in phenotypically similar organisms. E. lentum is characterized by nitrate reduction and enhanced growth in the presence of arginine. Many phenotypically similar organisms possess either one or the other of the two markers. In contrast, using the steroid-metabolizing enzymes as markers, a "steroid-active" and a "steroid-inactive" group were established with minimal overlapping of metabolic characteristics. Synthesis of the steroid enzymes was positively correlated with production of gas from H2O2 and formation of H2S. A simple method for the detection of corticoid 21-dehydroxylase and 3 alpha-hydroxysteroid dehydrogenase, one or both of which were present in 92% of the steroid-active group, is described.
Topics: 3-Hydroxysteroid Dehydrogenases; Bile Acids and Salts; Desoxycorticosterone; Eubacterium; Steroid 21-Hydroxylase; Steroid Hydroxylases
PubMed: 314778
DOI: 10.1128/aem.37.5.1001-1006.1979 -
Biomedicine & Pharmacotherapy =... Jan 2024Heart failure (HF) preserved ejection fraction (HFpEF) accounts for almost 50% of HF, and hypertension is one of the pathogenies. The MAPK signaling pathway is closely...
Heart failure (HF) preserved ejection fraction (HFpEF) accounts for almost 50% of HF, and hypertension is one of the pathogenies. The MAPK signaling pathway is closely linked to heart failure and hypertension; however, its function in HEpEF resulting from salt-sensitive hypertension is not well understood. In this work, a salt-sensitive hypertension-induced HEpEF model was established based on deoxycorticosterone acetate-salt (DOCA-salt) hypertension mice. The impact of the MAPK inhibitor (Doramapimod) on HEpEF induced by salt-sensitive hypertension was assessed through various measures, such as blood pressure, transthoracic echocardiography, running distance, and histological analysis, to determine its therapeutic effectiveness on cardiac function. In addition, the effects of high salt on myogenic cells were also evaluated in vitro using qRTPCR. The LV ejection fractions (LVEF) in DOCA-salt hypertension mice were over 50%, indicating that the salt-sensitive hypertension-induced HFpEF model was successful. RNA-seq revealed that the MAPK signaling pathway was upregulated in the HFpEF model compared with the normal mice, accompanied by hypertension, impaired running distance, restricted cardiac function, increased cross-sectional and fibrosis area, and upregulation of heart failure biomarkers, including GAL-3, LDHA and BNP. The application of Doramapimod could improve blood pressure, cardiomyocyte hypertrophy, and myocardial fibrosis, as well as decrease the aforementioned heart failure biomarkers. The qRTPCR results showed similar findings to these observations. Our findings suggest that the use of a MAPK inhibitor (Doramapimod) could be a potential treatment for salt-sensitive hypertension-induced HFpEF.
Topics: Mice; Animals; Heart Failure; Stroke Volume; Desoxycorticosterone Acetate; Cross-Sectional Studies; Hypertension; Sodium Chloride, Dietary; Fibrosis; Biomarkers
PubMed: 38056241
DOI: 10.1016/j.biopha.2023.115987 -
Kidney International May 1997
Review
Topics: Animals; Desoxycorticosterone; Diabetic Nephropathies; Fibrosis; Genetic Therapy; Glomerulonephritis; Graft Rejection; Humans; Kidney; Kidney Transplantation; Transforming Growth Factor beta
PubMed: 9150449
DOI: 10.1038/ki.1997.190 -
Kidney International Nov 1982
Review
Topics: Animals; Biological Transport; Catecholamines; Chlorides; Desoxycorticosterone; Electrolytes; Humans; In Vitro Techniques; Kidney Cortex; Kidney Medulla; Kidney Tubules; Kidney Tubules, Collecting; Potassium; Prostaglandins; Rabbits; Sodium; Vasopressins
PubMed: 6759755
DOI: 10.1038/ki.1982.200 -
Scientific Reports Jun 2016Inflammation plays an important role in the pathogenesis of hypertensive kidney disease. However, the molecular mechanisms underlying the induction of inflammation are...
Inflammation plays an important role in the pathogenesis of hypertensive kidney disease. However, the molecular mechanisms underlying the induction of inflammation are not completely understood. We have found that CXCL16 is induced in the kidney in deoxycorticosterone acetate (DOCA)-salt hypertension. Here we examined whether CXCL16 is involved in DOCA-salt-induced renal inflammation and fibrosis. Wild-type and CXCL16 knockout mice were subjected to uninephrectomy and DOCA-salt treatment for 3 weeks. There was no difference in blood pressure at baseline between wild-type and CXCL16 knockout mice. DOCA-salt treatment resulted in significant elevation in blood pressure that was comparable between wild-type and CXCL16 knockout mice. CXCL16 knockout mice exhibited less severe renal dysfunction, proteinuria, and fibrosis after DOCA-salt treatment compared with wild-type mice. CXCL16 deficiency attenuated extracellular matrix protein production and suppressed bone marrow-derived fibroblast accumulation and myofibroblast formation in the kidneys following DOCA-salt treatment. Furthermore, CXCL16 deficiency reduced macrophage and T cell infiltration into the kidneys in response to DOCA-salt hypertension. Taken together, our results indicate that CXCL16 plays a key role in the pathogenesis of renal injury and fibrosis in salt-sensitive hypertension through regulation of bone marrow-derived fibroblast accumulation and macrophage and T cell infiltration.
Topics: Acute Kidney Injury; Animals; Blood Pressure; Chemokine CXCL16; Desoxycorticosterone; Fibrosis; Hypertension, Renal; Mice; Mice, Knockout; Sodium Chloride, Dietary
PubMed: 27353044
DOI: 10.1038/srep28715 -
Postgraduate Medical Journal Apr 1953
Topics: Adrenal Cortex; Adrenal Cortex Diseases; Adrenal Insufficiency; Cortisone; Desoxycorticosterone; Humans
PubMed: 13055543
DOI: 10.1136/pgmj.29.330.215 -
The Journal of Clinical Investigation Jun 1994Uninephrectomized rats drinking 1% sodium chloride were given aldosterone (Aldo, 0.75 microgram/h, subcutaneous [s.c.] infusion), deoxycorticosterone (DOC, 20 mg/wk,...
Uninephrectomized rats drinking 1% sodium chloride were given aldosterone (Aldo, 0.75 microgram/h, subcutaneous [s.c.] infusion), deoxycorticosterone (DOC, 20 mg/wk, s.c.), corticosterone (B, 2 mg/d, s.c.), or the antiglucocorticoid-antiprogestin RU486 (2 mg/d, s.c.) for 8 wk, and hemodynamic and tissue responses were compared with a non-steroid-treated control group. Aldo and DOC markedly increased systolic BP and caused considerable (40-50%) cardiac hypertrophy; B and RU486 caused neither hypertension nor cardiac hypertrophy. Measurements of ventricular cross-sectional areas showed hypertrophy due to an increase in mass of the left ventricle only. Cardiac hydroxyproline concentration was increased considerably by Aldo and DOC, to a lesser degree by RU486, and not by B. Aldo markedly elevated left ventricular interstitial collagen (2.5-fold vs control, P < 0.01 vs all groups); other steroid treatments also increased interstitial collagen over control (DOC x 1.8-, RU486 x 1.6-, B x 1.3-fold), with identical responses for right and left ventricles (r = 0.94). A different pattern of perivascular fibrosis was noted; DOC elevated perivascular collagen (2.1-fold vs control, P < 0.01 vs all other groups); RU486 raised levels 1.4-fold vs control, but neither Aldo nor B significantly affected perivascular collagen. These data are consistent with interstitial cardiac fibrosis reflecting type I (mineralocorticoid) receptor occupancy by administered Aldo or DOC, or by elevated endogenous B after type II (glucocorticoid) receptor blockade after RU486 administration; perivascular fibrosis may reflect a composite response after type I receptor agonist/type II glucocorticoid receptor antagonist occupancy.
Topics: Aldosterone; Animals; Blood Pressure; Collagen; Desoxycorticosterone; Endomyocardial Fibrosis; Hydroxyproline; Hypertrophy, Left Ventricular; Male; Mifepristone; Rats; Rats, Sprague-Dawley
PubMed: 8200995
DOI: 10.1172/JCI117269