Search

The syndrome of 17α-hydroxylase deficiency is due to the inability to synthesize cortisol and is associated with enhanced secretion of both corticosterone and 11-deoxy-corticosterone (DOC). In humans, corticosterone and its 5α-Ring A-reduced metabolites are excreted via the bile into the intestine and transformed by anaerobic bacteria to 21-dehydroxylated products: 11β-OH-progesterone or 11β-OH-(allo)-5α-preganolones (potent inhibitors of 11β-HSD2 and 11β-HSD1 dehydrogenase). Neomycin blocks the formation of these steroid metabolites and can blunt the hypertension in rats induced by either ACTH or corticosterone. 3α,5α-Tetrahydro-corticosterone, 11β-hydroxy-progesterone, and 3α,5α-tetrahydro-11β-hydroxy-progesterone strongly inhibit 11β-HSD2 and 11β-HSD1 dehydrogenase activity; all these compounds are hypertensinogenic when infused in adrenally intact rats. Urine obtained from a patient with 17α-hydroxylase deficiency demonstrated markedly elevated levels of endogenous glycyrrhetinic acid-like factors (GALFs) that inhibit 11β-HSD2 and 11β-HSD1 dehydrogenase activity (>300 times greater, and >400 times greater, respectively, than those in normotensive controls). Thus, in addition to DOC, corticosterone and its 5α-pathway products as well as the 11-oxygenated progesterone derivatives may play a previously unrecognized role in the increased Na(+) retention and BP associated with patients with 17α-hydroxylase deficiency., (Copyright © 2013. Published by Elsevier Inc.)

Unlabelled: The study was carried out to appraise the serum total cholesterol, triglyceride, HDL-C and LDL-C values in hypertensive patients for providing information to the health-policy planners and also to the clinical practitioners about the importance of routine monitoring of lipid profile in hypertensive patients for prevention of coronary heart disease and other consequences to combat morbidity and mortality and to reinforce the need to consider these parameters in daily clinical practice. It was a cross-sectional study. The study was conducted at Department of Physiology and Biochemistry of Mymensingh Medical College, Medicine Unit of Mymensingh Medical College Hospital and in the community of Sadar, Mymensingh District. The period of the study was January 2005 to December 2005. A total number of seventy subjects were included in this study. Out of them 40 (forty) were hypertensive patients and 30 (thirty) were normotensive & healthy controls. Most of the hypertensive patients (65%) were taking treatment irregularly. Serum total cholesterol, serum triglyceride and serum LDL cholesterol were greater in hypertensive than those of normotensive . The differences of mean of serum total cholesterol, serum LDL cholesterol in between two groups were statistically significant and in case of serum triglyceride it was statistically highly significant. Serum HDL cholesterol was less in hypertensive than those of normotensive. The differences of mean of serum HDL cholesterol in between two groups were statistically highly significant. Among 40 hypertensives the number of "Getting treatment- regular" & "Getting treatment-irregular" was 14 (35%) & 26 (65%) respectively and the values are not statistically significant. Similarly in patients "suffering less than 5 years" and "suffering 5 years & above" the differences are also not statistically significant., Conclusion: The observations of this study has revealed that most of the hypertensive patients are taking treatment irregularly and there was significant alteration of serum cholesterol, triglyceride, HDL-C and LDL-C in hypertensive patients. Therefore, for routine monitoring of hypertensive patients to prevent the coronary heart disease (CHD) and other consequences, the reinforcement of the investigations of these parameters may be recommended in daily clinical practice.

Objective: Mechanisms of blood pressure (BP) regulation by endothelin (ET)-1 produced by endothelial cells are complex and remain unclear. Long-term exposure to human ET-1 (hET-1) in mice inducibly overexpressing hET-1 in the endothelium (ieET-1) caused sustained BP elevation. ET-1 has been shown to stimulate the release of aldosterone. Whether aldosterone plays a role in hET-1 overexpression-induced BP elevation and vessel injury is unknown., Method: Nine- to 12-week-old male ieET-1 mice and control mice expressing a tamoxifen-inducible Cre recombinase (CreERT2) in the endothelial cells (ieCre) were treated with tamoxifen for 5 days and studied 3 months later., Results: Endothelial hET-1 overexpression increased plasma aldosterone levels, which was reversed by 2-week treatment with atrasentan, an endothelin type A receptors blocker. Aldosterone synthase and cryptochrome 2 adrenal cortex mRNA expression was decreased in ieET-1 mice. Two-week treatment with eplerenone, a mineralocorticoid receptor antagonist, reduced systolic BP by 10 mmHg in ieET-1 mice during rest time. Saline challenge-induced sodium excretion and renal cortex thiazide-sensitive sodium-chloride cotransporter mRNA expression were decreased in ieET-1 mice. The sensitivity of mesenteric arteries to contraction by norepinephrine was increased in ieET-1 mice, and was abrogated by eplerenone treatment, whereas sensitivity of endothelium-independent relaxation responses to sodium nitroprusside was enhanced. Resistance artery remodeling was reduced in eplerenone-treated ieET-1 vs. ieET-1 and ieCre mice., Conclusion: These results demonstrate that aldosterone contributes to BP elevation and vascular norepinephrine sensitivity and remodeling caused by hET-1 overexpression in endothelium in mice., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: The study aims to verify the advantages of nonsteroidal mineralocorticoid receptor blockers (MRBs) in the management of hypertension and cardiovascular and renal diseases, comparing with conventional MRBs. Recent Findings: Based on the unique structures, the nonsteroidal MRBs have higher selectivity for mineralocorticoid receptors (MRs) and show no agonist activity for major steroid hormone receptors in contrast to steroidal MRBs. Today, there are two nonsteroidal MRBs, esaxerenone and finerenone, which completed phase 3 clinical trials. Series of clinical trials have shown that both agents achieve similar MR blockade with smaller doses as compared with steroidal MRBs, but have no off-target side effect such as gynecomastia. Esaxerenone has persistent blood pressure-lowering effects in various hypertensive populations, including essential hypertension and those with diabetes and/or chronic kidney disease, while finerenone has demonstrated reduction of the cardiovascular risk rather than blood pressure in patients with diabetes and chronic kidney disease. Summary: Nonsteroidal MRBs are a more refined agent which contributes to appropriate MR blocking with minimized unpleasant adverse effects. [ABSTRACT FROM AUTHOR]

Nonclassic apparent mineralocorticoid excess (NC-AME) is proposed as a novel clinical condition with a mild phenotypic spectrum that ranges from normotension to severe hypertension. This condition is mainly characterized by a high serum cortisol to cortisone ratio (F/E) and concomitant low cortisone (E), however further metabolic changes in NC-AME have not been studied. A cross-sectional study was performed in a primary-care cohort of 396 Chilean subjects, which were classified in two groups: NC-AME (n = 28) and healthy controls (n = 27). A discovery study based in untargeted metabolomics assay in serum samples from both groups was performed by UPLC-Q-TOF/MS. Global metabolomic variations were assayed by principal component analysis and further compared by orthogonal partial least-squares discriminant analysis (OPLS-DA). NC-AME subjects exhibited higher values of blood pressure, fractional excretion of potassium, and lower plasma renin activity and urinary sodium to potassium ratio. Metabolomic analyses showed 36 differentially regulated metabolites between NC-AME and control subjects. A ROC curve analyses identified eight metabolites with high discriminatory capacity between NC-AME and control subjects. Moreover, gamma-l-glutamyl-l-methionine sulfoxide and 5-sulfoxymethylfurfural, exhibited significant association with cortisone, which are potential biomarkers of NC-AME, however further assays should elucidate its biological role in setup and progression of this phenotype. [ABSTRACT FROM AUTHOR]

Intestinal bacteria can metabolize sterols, bile acids, steroid hormones, dietary proteins, fiber, foodstuffs, and short chain fatty acids. The metabolic products generated by some of these intestinal bacteria have been linked to a number of systemic diseases including obesity with Type 2 diabetes mellitus, some forms of inflammation, and more recently, systemic hypertension. In this review, we primarily focus on the potential role selected gut bacteria play in metabolizing the endogenous glucocorticoids corticosterone and cortisol. Those generated steroid metabolites, when reabsorbed in the intestine back into the circulation, produce biological effects most notably as inhibitors of 11α-hydroxysteroid dehydrogenase (11α-HSD) types 1 and 2. Inhibition of the dehydrogenase actions of 11α-HSD, particularly in kidney and vascular tissue, allows both corticosterone and cortisol the ability to bind to and activate mineralocorticoid receptors with attended changes in sodium handling and vascular resistance leading to increases in blood pressure. In several animal models of hypertension, administration of gut-cleansing antibiotics results in transient resolution of hypertension and transfer of intestinal contents from a hypertensive animal to a normotensive animal produces hypertension in the recipient. Moreover, fecal samples from hypertensive humans transplanted into germ-free mice resulted in hypertension in the recipient mice. Thus, it appears that the intestinal microbiome may not just be an innocent bystander but certain perturbations in the type and number of bacteria may directly or indirectly affect hypertension and other diseases. [ABSTRACT FROM AUTHOR]

Background: The association of CYP3A5 gene polymorphisms with hypertension in the Chinese population is unknown. We explored the association between the CYP3A5 (rs776746) gene and hypertension in the Chinese Han population.Methods: Using a case-control design, 340 cases and 254 controls were enrolled from the Third Affiliated Hospital of South Medical University between July and December of 2015. We used a standardized questionnaire to collect data regarding age, sex, smoking, drinking, family history of hypertension, and physical exercise. Height and weight were measured, and the body mass index (BMI) was calculated by weight/height2. Blood pressure was measured three times after 5 min of rest with at least 15 s between measurements, and the mean was considered the final BP. A Clinical examination was conducted.Results: A total of 594 participants, including 340 cases and 254 controls, were entered into the analyses. The genotype frequencies of the CYP3A5 G>A polymorphism did not deviate from the Hardy-Weinberg equilibrium. The genotype frequencies among the cases were 38.8% (GA, 132 individuals), 42.9% (GG, 146 individuals), and 18.2% (AA, 62 individuals). The differences in genotype between the cases and the controls were statistically significant. The AA genotype was associated with an elevated risk of hypertension after adjusting for potential confounders in Model 2. There was no interaction between smoking and the CYP3A5 genotype, while the interaction between drinking and the CYP3A5 genotype was significant.Conclusion: The CYP3A5 gene may be associated with the risk of hypertension in the Chinese Han population, and this effect may be exacerbated by drinking. [ABSTRACT FROM AUTHOR]

Purpose of the Review: Evidence is rapidly accumulating implicating gut dysbiosis in hypertension (HTN). However, we are far from understanding whether this is a cause or consequence of HTN, and how to best translate this fundamental knowledge to advance the management of HTN. This review aims to summarize recent advances in the field, illustrate the connections between the gut and hypertension, and establish that the gut microbiota (GM)-gut interaction is centrally positioned for consideration as an innovative approach for HTN therapeutics. Recent Findings: Animal models of HTN have shown that gut pathology occurs in HTN, and provides some clues to mechanisms linking the dysbiosis, gut pathology, and HTN. Summary: Circumstantial evidence links gut dysbiosis and HTN. Gut pathology, apparent in animal HTN models, has not been fully investigated in hypertensive patients. Objective evidence and an understanding of mechanisms could have a major impact for new antihypertensive therapies and/or improved applications of current ones. [ABSTRACT FROM AUTHOR]

Hypertension is one of the most common problems encountered in the primary care setting. Numerous secondary causes of hypertension exist and are potentially reversible. The ability to screen for such causes and manage them effectively may spare patients from prolonged medical therapy and hypertensive complications. Licorice can cause hypertension and hypokalemia due its effects on cortisol metabolism. We report a case of jelly bean ingestion that highlights the presentation, pathophysiology and management of licorice-induced hypertension. [ABSTRACT FROM PUBLISHER]

As a major cardiovascular risk factor for stroke, coronary artery disease, heart failure and end-stage renal disease, hypertension affects approximately one billion people and causes large economic burden worldwide. Cytochrome P450 3A5 (CYP3A5), belonging to the CYP3A subfamily, has been implicated in the regulation of blood pressure and may serve as a potential risk factor for the development of hypertension. Increased CYP3A5 activity could cause sodium and water retention by affecting the metabolism of cortisol in the kidneys. Furthermore, polymorphic CYP3A5 genotypes have been shown to cause differences in blood pressure response to antihypertensive drugs. Several studies have investigated the role of CYP3A5 in blood pressure response to amlodipine. However, recent data on the role of CYP3A5 in hypertension development and treatment are inconsistent. This review summarizes what is known regarding the relationship of CYP3A5 with hypertension, discusses the limitations in present studies, highlights the gaps and directs research to this field. [ABSTRACT FROM AUTHOR]

BACKGROUND Impairment in 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity results in inefficient inactivation of cortisol to cortisone, and it can trigger hypertension through activation of the mineralocorticoid receptor. Information about age-related changes in 11β-HSD2 activity and its physiological consequences is scarce. Our aim was to investigate whether 11β-HSD2 activity is age dependent in normotensive subjects. METHODS We recruited 196 healthy, normotensive subjects. Of these, 93 were children (Group 1: aged 5–15 years), and 103 were adults who were divided according to their ages: Group 2: aged 30–41 years (n = 10); Group 3: aged 42–53 years (n = 72); and Group 4: aged 54–65 years (n = 21). Fasting serum cortisol, cortisone, aldosterone, and plasma renin activity (PRA) were measured. The 11β-HSD2 activity was estimated by the cortisol/cortisone ratio. The results were expressed as median (interquartile range (IQR)) values and compared using Kruskal–Wallis and Dunn’s multiple-comparison tests. RESULTS As subject age increased, cortisol concentrations increased (Group 1 median = 8.6, IQR = 6.3–10.8 µg/dl; Group 4 median = 12.4, IQR = 10.7–14.7 µg/dl; P < 0.001), and cortisone concentrations showed a gradual decrease (Group 2 median = 4.0, IQR = 3.3–4.2 µg/dl; Group 4 median =2.8, IQR = 2.6–3.3 µg/dl; P < 0.01). As a consequence, the cortisol/cortisone ratio was higher in the oldest subjects (Group 4) than in the subjects from the other 3 groups; the ratios from Group 4 to Group 1 were 4.4 (IQR = 3.7–5.1) µg/dl, 3.3 (IQR = 2.7–3.8) µg/dl, 2.5 (IQR = 2.3–3.8) µg/dl, and 2.7 (IQR = 2.1–3.4) µg/dl, respectively (P < 0.01). The PRA decreased with age. Blood pressure levels increased with age but stayed within the normal range. CONCLUSIONS Cortisol and the cortisol/cortisone ratio increased with age, but cortisone decreased, suggesting a decrease in 11β-HSD2 activity. These results suggest that the cortisol-mediated activation of the mineralocorticoid receptor may explain the blood pressure increase in elderly subjects. [ABSTRACT FROM AUTHOR]

Renal allograft donors are at risk of developing hypertension. Here, we hypothesized that this risk is at least in part explained by an enhanced intracellular availability of 11&bgr;-hydroxyglucocorticoids due to an increased 11&bgr;-hydroxysteroid dehydrogenase type 1 enzyme (11&bgr;-HSD1), an intracellular prereceptor activator of biologically inactive 11-ketocorticosteroids in the liver, and/or a diminished 11&bgr;-hydroxysteroid dehydrogenase type 2 (11&bgr;-HSD2), an inactivator of 11&bgr;-hydroxyglucocorticoids in the kidney. To test this hypothesis, uninephrectomized (UNX) (nZ9) and sham-operated (nZ10) adult Sprague- Dawley rats were investigated. Mean arterial blood pressure and heart rate were measured continuously by telemetry for 6 days in week 5 after UNX. The mRNA of 11&bgr;-Hsd1 and 11&bgr;-Hsd2 in liver and kidney tissues were assessed by RT-PCR and the 11&bgr;-HSD activities were directly quantified in their corresponding tissues by determining the ratios of (tetrahydrocorticosteroneC5a-tetrahydrocorticosterone)/ tetrahydrodehydrocorticosterone ((THBC5a-THB)/THA) and of corticosterone/dehydrocorticosterone (B/A) by gas chromatography-mass spectrometry. The apparent total body activities of 11&bgr;-HSD1 and 11&bgr;-HSD2 were estimated using the urinary and plasma ratios of (THB+5&agr;-THB)/THA and B/A. Mean arterial blood pressure was increased after UNX when compared with sham operation. Hepatic mRNA content of 11&bgr;-Hsd1 and hepatic, plasma, and urinary ratios of (THB+5&agr;-THB)/THA were decreased after UNX, indicating diminished access of glucocorticoids to its receptors. In renal tissue, 11&bgr;-Hsd2 mRNAwas reduced and B/A ratios measured in kidney, plasma, and urine were increased, indicating reduced 11&bgr;-HSD2 activity and enhanced access of glucocorticoids to mineralocorticoid receptors. Both 11&bgr;-HSD1 and 11&bgr;-HSD2 are downregulated after UNX in rats, a constellation considered to induce hypertension. [ABSTRACT FROM AUTHOR]

19-nor-progesterone (19-nor-P) has the characteristics of a potent mineralocorticoid in adrenalectomized or salt-loaded rats and is capable of causing hypertension. In human placenta, progesterone is converted to 19-hydroxy-progesterone, a precursor of 19-nor-P. In some states of pregnancy hypertension, 19-nor-P may inhibit renal 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), thus allowing cortisol to bind to the mineralocorticoid receptor (MR). Therefore, we investigated the ability of 19-nor-P to inhibit human 11β-HSD2. Fetal kidney cells (HEK 293) were transfected with human 11β-HSD2 and incubated with increasing concentrations of 19-nor-P, labelled and unlabelled cortisol. Steroids were extracted, separated by TLC, and radioactivity was measured using a TLC scanner. 19-nor-P treatment did not significantly reduce 11β-HSD2 activity (430 to 300 pmol/mg protein/h) in the range of tested concentrations. In conclusion, 19-nor-P did not inhibit human 11β-HSD2 and seems not to be involved in human hypertension. Nevertheless, 19-nor-P may be converted by extra-adrenal tissues into 19-nor-deoxycorticosterone (DOC) or 19-nor-corticosterone, which are potent mineralocorticoids and may be involved in the pathogenesis of hypertension during pregnancy. [ABSTRACT FROM AUTHOR]