Glucocorticoids and blood pressure: a role for the cortisol/cortisone shuttle in the control of vascular tone in man

Walker, Brian R.; Connacher, A. A.; Webb, David J.; Edwards, C. R. W.

doi:10.1042/cs0830171

Cited by 116 publications

(51 citation statements)

References 14 publications

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“…The influence of 11b-HSDs on vascular function has been addressed using non-selective enzyme inhibitors (80)(81)(82)(83), antisense knockdown (84) and in global 'knockout' mice (68,85) but not yet by cell-specific manipulations of 11b-HSDs. While loss of 11b-HSD2 dehydrogenase inactivation of glucocorticoid in the endothelium was associated with enhanced vasoconstrictor responses, loss of 11b-HSD1 reductase regeneration of glucocorticoid in vascular smooth muscle did not influence vascular tone.…”

Section: Glucocorticoid Signalling In Cardiovascular Organsmentioning

confidence: 99%

Glucocorticoids and Cardiovascular Disease

Walker¹

2007

European Journal of Endocrinology

470

394

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Chronic excessive activation of glucocorticoid receptors induces obesity, insulin resistance, glucose intolerance, dyslipidaemia and hypertension. Subtle abnormalities of the hypothalamic-pituitaryadrenal axis and/or of tissue sensitivity to glucocorticoids are also associated with these cardiovascular risk factors in patients with the metabolic syndrome. Furthermore, glucocorticoids have direct effects on the heart and blood vessels, mediated by both glucocorticoid and mineralocorticoid receptors and modified by local metabolism of glucocorticoids by the 11b-hydroxysteroid dehydrogenase enzymes. These effects influence vascular function, atherogenesis and vascular remodelling following intravascular injury or ischaemia. This article reviews the systemic and cardiovascular effects of glucocorticoids, and the evidence that glucocorticoids not only promote the incidence and progression of atherogenesis but also modify the recovery from occlusive vascular events and intravascular injury. The conclusion is that manipulation of glucocorticoid action within metabolic and cardiovascular tissues may provide novel therapeutic avenues to combat cardiovascular disease.European Journal of Endocrinology 157 545-559

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Section: Glucocorticoid Signalling In Cardiovascular Organsmentioning

confidence: 99%

Glucocorticoids and Cardiovascular Disease

Walker¹

2007

European Journal of Endocrinology

470

394

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“…First, glucocorticoid decreased the blood flow by inhibiting the production of prostaglandin I2 which is a vasodilator [7]. It also maintained the vascular tone in forearm artery by potentiating vascular responses to noradrenaline [8,9]. Some researches indicated that glucocorticoids control the blood pressure in rats through increasing the sensitivity of alpha 1-adrenergic receptors to norepinephrine [10].…”

Section: Discussionmentioning

confidence: 99%

Intratympanic Dexamethasone on Cochlear Blood Flow in Guinea Pigs

Chiang

Yeh

Chiang

et al. 2012

Indian J Otolaryngol Head Neck Surg

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To determine the effect of intratympanically delivered dexamethasone on cochlear blood flow. 29 white Hartly guinea pigs were divided into 2 groups. By laser Doppler flowmeter, baseline data were recorded in the first 15-20 min, followed by 20 min' recording after applying dexamethasone or normal saline, with a record of flow every 5 min in 2 groups. Friedman Test was used to test the change of blood flow in these four timing. There were no significant changes of blood flow after injecting dexamethasone (p = .18 [ .05) and normal saline (p = .93 [ .05). The effects of dexamethasone on cochlear blood flow were variable and not significant. The following research would be designed under pathological conditions, such as cochlear ischemia, to show the possible mechanism of dexamethasone for specific inner ear disease. Level of evidence: 3a (SR of case-control studies).

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“…In vitro and in vivo studies indicate that 11 -HSDs regulate vascular tone at an autocrine level through the amplification of responses to vasoconstrictors (49). Inhibition of 11 -HSD2 in vascular smooth muscle cells resulted in increased responses to angiotensin-II (50) and phenylephrine (51).…”

Section: -Hsd2 and "Essential" Hypertensionmentioning

confidence: 99%

Apparent mineralocorticoid excess syndrome: an overview

Palermo

Quinkler

Stewart

2004

Arq Bras Endocrinol Metab

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Apparent mineralocorticoid excess (AME) syndrome results from defective 11 -hydroxysteroid dehydrogenase type 2 (11 -HSD2). This enzyme is co-expressed with the mineralocorticoid receptor (MR) in the kidney and converts cortisol (F) to its inactive metabolite cortisone (E). Its deficiency allows the unmetabolized cortisol to bind to the MR inducing sodium retention, hypokalemia, suppression of PRA and hypertension. Mutations in the gene encoding 11 -HSD2 account for the inherited form, but a similar clinical picture to AME occurs following the ingestion of bioflavonoids, licorice and carbenoxolone, which are competitive inhibitors of 11 -HSD2. Reduced 11 -HSD2 activity may explain the increased sodium retention in preeclampsia, renal disease and liver cirrhosis. Relative deficiency of 11 -HSD2 activity can occur in Cushing's syndrome due to saturation of the enzyme and explains the mineralocorticoid excess state that characterizes ectopic ACTH syndrome. Reduced placental 11 -HSD2 expression might explain the link between reduced birth weight and adult hypertension. Polymorphic variability in the HSD11B2 gene in part determines salt sensitivity, a forerunner for adult hypertension onset. AME represents a spectrum of mineralocorticoid hypertension with severity reflecting the underlying genetic defect in the 11 -HSD2; although AME is a genetic disorder, several exogenous compounds can bring about the symptoms by inhibiting 11 -HSD2 enzyme. Substrate excess as seen in Cushing's syndrome and ACTH ectopic production can overwhelm the capacity of 11 -HSD2 to convert F to E, leading up to an acquired form of AME. A síndrome do excesso aparente de mineralocorticóides (SEAM) resulta de defeito na 11 -hidroxisteróide desidrogenase tipo 2 (11 -HSD2). Esta enzima é co-expressa com o receptor mineralocorticóide (RM) nos rins e converte cortisol (F) em cortisona (E), seu metabólito inativo. Deficiência desta enzima permite que o cortisol não metabolizado se ligue ao RM, induzindo retenção de sódio, hipocalemia, supressão da APR e hipertensão. Mutações no gene que codifica a 11 -HSD2 são responsáveis pela forma herdada, mas um quadro clínico semelhante de SEAM ocorre durante ingestão dos bioflavonóides, alcaçuz e carbenoxolona, que são inibidores competitivos da 11 -HSD2. Redução na atividade da 11 -HSD2 pode explicar o aumento da retenção de sódio na pré-eclâmpsia, na doença renal e na cirrose hepática. Deficiência relativa de atividade da 11 -HSD2 pode ocorrer na síndrome de Cushing devido à saturação da enzima e explicar o estado de excesso mineralocorticóide que caracteriza a síndrome do ACTH ectópico. Redução da expressão placentária da 11 -HSD2 poderia justificar a ligação entre baixo peso ao nascer e hipertensão no adulto. Variabili-

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Glucocorticoids and blood pressure: a role for the cortisol/cortisone shuttle in the control of vascular tone in man

Cited by 116 publications

References 14 publications

Glucocorticoids and Cardiovascular Disease

Glucocorticoids and Cardiovascular Disease

Intratympanic Dexamethasone on Cochlear Blood Flow in Guinea Pigs

Apparent mineralocorticoid excess syndrome: an overview

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