11β-Hydroxysteroid Dehydrogenases and Hypertension in the Metabolic Syndrome.

Existing Reviews

Please note, new claims can take a short while to show up.

No claims yet.

Annotation Summary

Term Occurence Count Dictionary
apparent mineralocorticoid excess 1 endocrinologydiseases
cortisol 11 endocrinologydiseasesdrugs
dexamethasone 3 endocrinologydiseasesdrugs
hypokalemia 1 endocrinologydiseases
metabolic syndrome 30 endocrinologydiseases
obesity 3 endocrinologydiseases
spironolactone 1 endocrinologydiseasesdrugs

Graph of close proximity drug and disease terms (within 200 characters).

Note: If this graph is empty, then there are no terms that meet the proximity constraint.

Review

Having read the paper, please pick a pair of statements from the paper to indicate that a drug and disease are related.

Select Drug Character Offset Drug Term Instance
cortisol 850 excess is a key causal feature of metabolic syndrome. This is not increased systemic in circulating cortisol , rather increased bioavailability of active glucocorticoids within tissues. This review examines the
cortisol 4103 of Cushing syndrome displays the same key features as metabolic syndrome [[]]. Although circulating cortisol is not elevated in most patients with metabolic syndrome, “glucocorticoid excess” is a complex concept
cortisol 5091 metabolic syndrome.11βHSDs and Glucocorticoid SignallingPlasma concentrations of active glucocorticoid ( cortisol in humans; corticosterone in rodents) are determined by the balance between synthesis and clearance,
cortisol 5716 (cortisone in humans; 11-dehydrocorticosterone in rodents) by 11βHSD1 (see [[]•] for review). Systemic cortisol clearance is primarily mediated by hepatic 5α- and 5β-reductases, with a significant contribution
cortisol 6123 is regulated by enzymatic modification of the C11 side chain. In humans, the reduced 11-hydroxy form cortisol (F) is physiologically active at the mineralocorticoid receptor; the oxidised 11-keto form cortisone
cortisol 6903 glucocorticoids in vivo. The changes in redox potential that accompany NAD+ metabolism may lock MR- cortisol complexes in an inactive stateThe 11βHSD enzymes have conventionally been regarded as regulators of
cortisol 7210 concentration of glucocorticoid is not affected by deletion of 11βHSD2 [[]], but the half-life of cortisol is increased in patients with null mutations in the encoding gene, HSD11B2. The effect of 11βHSD1 deletion
cortisol 8067 “cellular” view lacks nuance: in humans, 11βHSD1 activity contributes to the postprandial rise in plasma cortisol [[]] and in mice 11βHSD2 activity influences the relationship between dietary salt intake and circulating
cortisol 8979 syndrome has been extensively reviewed [[]]. Mechanistically, chronic (5-day) infusion of either ACTH or cortisol into healthy men causes antinatriuresis and volume expansion [[]]. Studies in mice show activation of
cortisol 19739 the enzyme by glycerrhetinic acid such as found in liquorice [[]], would permit activation of MR by cortisol (or corticosterone in rodent models), causing sodium retention [[]] due to enhanced reabsorption in
cortisol 23603 syndrome status [[]••]. This study was observational, and the association between dietary salt intake, cortisol production, and metabolic disease cannot be regarded as causal. Nevertheless, these relationships have
dexamethasone 9333 conditional deletion of GR in the distal nephron does not blunt the hypertensive response to chronic dexamethasone [[]] (a synthetic glucocorticoid) and long-term glucocorticoid excess causes volume contraction rather
dexamethasone 9684 [[]]: mice with conditional deletion of GR in the vascular endothelium are partially protected against dexamethasone -hypertension [[]]. Nevertheless, it is likely that blood pressure control by the kidney is impaired:
dexamethasone 17672 physiological glucocorticoid excess. However, recent data from our lab indicate that high doses of dexamethasone actually reduce renal Hsd11b2 expression [[]]. Studies in obese humans also find impaired renal 11βHSD2
spironolactone 20312 salt-sensitive hypertension was prevented by GR blockade with RU486 rather than by MR blockade with spironolactone [[], []]. The relationship between 11βHSD2, GR, and MR appears to be more complex than previously thought,
Select Disease Character Offset Disease Term Instance
apparent mineralocorticoid excess 17178 important for blood pressure control. Congenital or acquired deficiency in 11βHSD2 causes the syndrome of apparent mineralocorticoid excess (AME; OMIM #218030), presenting with salt retention, potassium wasting, and hypertension [[]].Renal
hypokalemia 10146 hypertension in ACTH or glucocorticoids excess is often associated with electrolyte abnormalities (e.g. hypokalemia ) suggestive of aldosterone excess and in mice ACTH induces increased renal transcription of aldosterone-response
metabolic syndrome 242 date (epub): 11/2017Publication date (pmc-release): 11/2017Publication date (ppub): /2017AbstractThe metabolic syndrome describes a clustering of risk factors—visceral obesity, dyslipidaemia, insulin resistance, and salt-sensitive
metabolic syndrome 592 fatty liver disease. The prevalence of these concurrent comorbidities is ~ 25–30% worldwide, and metabolic syndrome therefore presents a significant global public health burden. Evidence from clinical and preclinical
metabolic syndrome 784 from clinical and preclinical studies indicates that glucocorticoid excess is a key causal feature of metabolic syndrome . This is not increased systemic in circulating cortisol, rather increased bioavailability of active
metabolic syndrome 1024 within tissues. This review examines the role of covert glucocorticoid excess on the hypertension of the metabolic syndrome . Here, the role of the 11β-hydroxysteroid dehydrogenase enzymes, which exert intracrine and paracrine
metabolic syndrome 1587 promotes salt retention and hypertension. As for hypertension in general, high blood pressure in the metabolic syndrome reflects a complex interaction between multiple systems. The clear association between high dietary
metabolic syndrome 1851 metabolic disorders has major relevance for human health and warrants systematic evaluation.IntroductionThe metabolic syndrome describes a concurrence of interrelated abnormalities, including visceral obesity, dyslipidaemia, insulin
metabolic syndrome 2158 significant cardiovascular risk. In combination, the risk is amplified, and all-cause mortality increases: metabolic syndrome predicts the development of type 2 diabetes, cardiovascular disease, cancer, and non-alcoholic fatty
metabolic syndrome 2340 disease, cancer, and non-alcoholic fatty liver disease [[]]. Although a single, unifying definition of metabolic syndrome is lacking, the prevalence of these concurrent comorbidities is ~ 25–30% worldwide [[]], presenting
metabolic syndrome 2781 beyond management of individual components. For example, hypertension is one of the cardinal features of metabolic syndrome , but the origins of high blood pressure are obscure and lost in the complexity of the syndrome. Clearly
metabolic syndrome 2904 the origins of high blood pressure are obscure and lost in the complexity of the syndrome. Clearly metabolic syndrome captures a cluster of pathophysiological features that are individually accepted as “pro-hypertensive”:
metabolic syndrome 3275 system [[]], sympathetic overdrive [[]], and oxidative stress [[]]. These have all been described in metabolic syndrome patients (and in animal models), as they have for uncomplicated hypertension. Indeed, as for uncomplicated
metabolic syndrome 3541 individual component is “causal”, and there is no distinct blood pressure management strategy for metabolic syndrome patients. Lifestyle and nutritional interventions to increase calorific outflow and lower salt intake
metabolic syndrome 3820 control requires early therapeutic intervention [[]]. Nevertheless, there are interesting aspects to metabolic syndrome that may offer a route to improve blood pressure control. Glucocorticoids are important regulators of
metabolic syndrome 4057 Although rare, the systemic glucocorticoid excess of Cushing syndrome displays the same key features as metabolic syndrome [[]]. Although circulating cortisol is not elevated in most patients with metabolic syndrome, “glucocorticoid
metabolic syndrome 4150 features as metabolic syndrome [[]]. Although circulating cortisol is not elevated in most patients with metabolic syndrome , “glucocorticoid excess” is a complex concept and may instead reflect instead amplification of cellular
metabolic syndrome 4986 concluding by addressing the potential therapeutic relevance to the management of patients with the metabolic syndrome .11βHSDs and Glucocorticoid SignallingPlasma concentrations of active glucocorticoid (cortisol in humans;
metabolic syndrome 11230 also offers cardiovascular benefits independent of blood pressure control. In a novel rat model of metabolic syndrome , generated by intercross between Dahl-salt-sensitive and Zuker obese rats, RU486 reduced adiposity,
metabolic syndrome 12028 11βHSD1 and consequent intracellular glucocorticoid amplification is similarly reported in patients with metabolic syndrome [[]]. Transgenic approaches strongly evidence the relationship between adipose 11βHSD1 and metabolic
metabolic syndrome 12554 cellular glucocorticoid, without changing circulating corticosterone levels, and induces a comprehensive metabolic syndrome phenotype [[]]. Importantly, these overexpressing mice have the salt-sensitive hypertension and attenuation
metabolic syndrome 12771 attenuation of the normal sleep-phase dip [[]], characteristic of the blood pressure profile in human metabolic syndrome . In the mice, cellular amplification of corticosterone increased production of angiotensinogen by adipocytes,
metabolic syndrome 13010 the systemic RAAS [[]]. Blood pressure was normalised with an angiotensin receptor blocker, and in metabolic syndrome patients, ARBs offer a safe, effective, and well-tolerated means of blood pressure control [[]], with
metabolic syndrome 13580 blood pressure in non-obese people [[]–[]]. This SNP associates with type 2 diabetes but not with the metabolic syndrome [[]], and such studies offer limited mechanistic insight. However, 11βHSD1 is expressed in systems
metabolic syndrome 14117 (resistance) or thoracic aorta [[]]. Recent studies show that 11βHSD1 in perivascular fat, amplified in metabolic syndrome [[]•], can influence vascular tone: sympathetic over activation increased 11βHSD1 activity and glucocorticoid
metabolic syndrome 16489 reduction in blood pressure as a secondary endpoint in patients with either type 2 diabetes or the metabolic syndrome [[]•]. This was not statistically significant when assessed as a primary endpoint in obese patients
metabolic syndrome 21885 physiologically regulated by glucocorticoid. Clearly, this has implications for blood pressure regulation in the metabolic syndrome , where local glucocorticoid excess may underpin enhanced sodium reabsorption in the distal nephron.
metabolic syndrome 22059 enhanced sodium reabsorption in the distal nephron. High-fat feeding to mice recapitulates key features of metabolic syndrome . Impaired sodium excretion and salt-sensitive hypertension reflect activation of furosemide-sensitive
metabolic syndrome 22375 circulating or intracellular glucocorticoids are common and often associated with hypertension. The metabolic syndrome exemplifies the complexity of glucocorticoid-dependent hypertension: clinical investigation and studies
metabolic syndrome 22665 homeostatic systems controlling blood pressure (Fig. 2). A unifying factor is that hypertension in the metabolic syndrome is commonly salt-sensitive. This presents a major challenge for clinical management, since salt intake
metabolic syndrome 23486 metabolism [[]]. Importantly, this relationship between salt intake and glucocorticoid production predicted metabolic syndrome status [[]••]. This study was observational, and the association between dietary salt intake, cortisol
metabolic syndrome 23862 warrant systematic evaluation.Fig. 2Mechanisms contributing to systemic arterial hypertension in the metabolic syndrome . Hypertension is salt-sensitive and reflects renal, vascular, and central mechanisms. The concept that
obesity 311 date (ppub): /2017AbstractThe metabolic syndrome describes a clustering of risk factors—visceral obesity , dyslipidaemia, insulin resistance, and salt-sensitive hypertension—that increases mortality related
obesity 1944 evaluation.IntroductionThe metabolic syndrome describes a concurrence of interrelated abnormalities, including visceral obesity , dyslipidaemia, insulin resistance, and hypertension. Each of these features independently carries significant
obesity 18956 sodium balance is restored: activation of the MR target protein ENaC, increases vascular stiffness in obesity [[]]. In the CNS, 11βHSD2 is expressed in a subset of neurons in the nucleus of the solitary tract.

You must be authorized to submit a review.