Glucocorticoids and the kidney

Mangos, George; Whitworth, Judith A.; Williamson, Paula; Kelly, John J.

doi:10.1111/j.1440-1797.2003.00215.x

Cited by 50 publications

(36 citation statements)

References 86 publications

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“…Clinical experience demonstrates that the hypertension induced by steroids occurs much too rapidly to be accounted for solely, if at all, by increased renal sodium reabsorption. 1,24 In addition, in animal models, mineralocorticoid antagonists such as spironolactone prevent GC-induced weight gain but do not prevent HTN. 25,26 Excess renal salt reabsorption does not seem to be required for GC to induce HTN, 1 and DEX and budesonide, synthetic GC with increased affinity for GR and decreased affinity for MR, induce sustained HTN similar to that observed with endogenous GC.…”

Section: Discussionmentioning

confidence: 99%

“…1,24 In addition, in animal models, mineralocorticoid antagonists such as spironolactone prevent GC-induced weight gain but do not prevent HTN. 25,26 Excess renal salt reabsorption does not seem to be required for GC to induce HTN, 1 and DEX and budesonide, synthetic GC with increased affinity for GR and decreased affinity for MR, induce sustained HTN similar to that observed with endogenous GC. 27,28 These points argue convincingly that GC have a wide range of hemodynamic effects distinct from their presumed activation of renal MR, thus increasing the understanding of the role of GR in the regulation of BP is of interest.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3] The lack of understanding of the underlying mechanisms of GC-induced HTN leads to empiric and often suboptimal treatment of this common clinical condition. Although traditionally GC have commonly been believed to increase BP via promiscuous activation of the mineralocorticoid receptor (MR) in the kidney, 4,5 available data argue that this is not the only or perhaps even the primary mechanism underlying this form of HTN.…”

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confidence: 99%

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A Critical Role for Vascular Smooth Muscle in Acute Glucocorticoid-Induced Hypertension

Goodwin¹,

Zhang²,

Geller³

2008

Journal of the American Society of Nephrology

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Although glucocorticoid (GC)-induced hypertension has commonly been attributed to promiscuous activation of the mineralocorticoid receptor by cortisol, thereby promoting excess reabsorption of sodium and water, numerous lines of evidence indicate that this is not the only or perhaps even the primary mechanism. GC induce a number of effects on vascular smooth muscle (VSM) in vitro that may be pertinent to hypertension, but their contribution in vivo is unknown. To address this question, a mouse model with a tissue-specific knockout (KO) of the GC receptor in the VSM was created and characterized. Similar to control mice, KO mice exhibited normal baseline BP and, interestingly, showed normal circadian variation in BP. When dexamethasone was administered, however, the acute hypertensive response was markedly attenuated in KO mice, and there was a trend toward a decreased chronic hypertensive response. These data suggest that the GC receptor in VSM plays a critical role in the acute hypertensive response to GC in vivo.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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A Critical Role for Vascular Smooth Muscle in Acute Glucocorticoid-Induced Hypertension

Goodwin¹,

Zhang²,

Geller³

2008

Journal of the American Society of Nephrology

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“…Glucocorticoids, whether endogenous, as in Cushing syndrome, or exogenous, via pharmacologic provision, induce hypertension (Mangos et al 2003). They directly stimulate NHE3 through both acute and chronic mechanisms (Bobulescu and Moe 2009).…”

Section: Glucocorticoidsmentioning

confidence: 99%

Hormonal Actions and Interactions in Proximal Tubule Cells Associated with the Development of Chronic Kidney Disease

Saito¹,

Hosojima²,

Sato³

2011

Basic and Clinical Endocrinology Up-to-Date

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“…Cortisol, the endogenous glucocorticoid, can produce hypertension associated with increased sodium and water retention and cause renal impairment via interaction with both mineralocorticoid and glucocorticoid receptors (Whitworth et al, 1989(Whitworth et al, , 2000Mangos et al, 2003). DEX, in contrast, affects renal function (Bia et al, 1982) specifically via the glucocorticoid receptor (GR) (Reul et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

A Novel Model of Dexamethasone-Induced Hypertension: Use in Investigating the Role of Tyrosine Hydroxylase

Soto‐Piña

Franklin

Rani

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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Our objective was to study hypertension induced by chronic administration of synthetic glucocorticoid, dexamethasone (DEX), under nonstressful conditions and examine the role of catecholamine biosynthesis. To achieve this, we did the following: 1) used radiotelemetry to record mean arterial pressure (MAP) and heart rate (HR) in freely moving rats, and 2) administered different doses of DEX in drinking water. To evaluate the involvement of tyrosine hydroxylase (TH), the rate-limiting step in catecholamine biosynthesis, we treated rats with the TH inhibitor, a-methyl-paratyrosine (a-MPT), for 3 days prior to administration of DEX and assessed TH mRNA and protein expression by quantitative realtime polymerase chain reaction and Western blot in the adrenal medulla. We observed a dose-dependent elevation in blood pressure with a DEX dose of 0.3 mg/kg administered for 10 days, significantly increasing MAP by 115.0 6 1.1 mm Hg, while concomitantly reducing HR. Although this DEX treatment also significantly decreased body weight, pair-fed animals that showed similar decreases in body weight due to lowered food intake were not hypertensive, suggesting that body weight changes may not account for DEX-induced hypertension. Chronic DEX treatment significantly increased the TH mRNA and protein levels in the adrenal medulla, and a-MPT administration not only reduced DEX pressor effects, but also inhibited TH (serine 40 ) phosphorylation. Our study thus validates a novel model to study hypertension induced by chronic intake of DEX in freely moving rats not subject to the confounding factors of previous models and establishes its dependence on concomitant activation of peripheral catecholamine biosynthesis.

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Glucocorticoids and the kidney

Cited by 50 publications

References 86 publications

A Critical Role for Vascular Smooth Muscle in Acute Glucocorticoid-Induced Hypertension

A Critical Role for Vascular Smooth Muscle in Acute Glucocorticoid-Induced Hypertension

Hormonal Actions and Interactions in Proximal Tubule Cells Associated with the Development of Chronic Kidney Disease

A Novel Model of Dexamethasone-Induced Hypertension: Use in Investigating the Role of Tyrosine Hydroxylase

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