Induction by Glucocorticoids of Angiotensin Converting Enzyme Production from Bovine Endothelial Cells in Culture and Rat Lung In Vivo

Mendelsohn, Frederick A.O.; Lloyd, Christopher J.; Kachel, Christine D.; Funder, John W.

doi:10.1172/jci110663

Cited by 130 publications

(56 citation statements)

References 30 publications

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“…This hypothesis is based on previous studies in cultured cells: glucocorticoids induce an increase in NEP gene expression and in NEP activity in cultured human airway epithelial cells (10). Similarly, glucocorticoids induce ACE activity in cultures ofrabbit alveolar macrophages (1 1), bovine endothelial cells (12), and human monocytes (32). Pretreatment with dexamethasone results in an increase of ACE activity in homogenates of rat lungs (12).…”

Section: Discussionmentioning

confidence: 95%

See 1 more Smart Citation

Neutral endopeptidase and kininase II mediate glucocorticoid inhibition of neurogenic inflammation in the rat trachea.

Piedimonte¹,

McDonald²,

Nadel³

1991

J. Clin. Invest.

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Glucocorticoids inhibit plasma extravasation induced in the rat tracheal mucosa by substance P and other tachykinins released from sensory nerves. This study was performed to determine whether this antiinflammatory effect of glucocorticoids is mediated by the tachykinin-degrading enzymes neutral endopeptidase (NEP) and kininase II (angiotensin converting enzyme, ACE). In addition, we studied the effect of dexamethasone on a nonpeptide inflammatory mediator, platelet-activating factor (PAF), which is not degraded by NEP or ACE. Adult male pathogen-free F344 rats were treated for 2 d with dexamethasone (0.5 mg/kg per d i.p.), or with the vehicle used to dissolve the steroid. The magnitude of plasma extravasation produced by an intravenous injection of substance P (5 Mg/kg) or PAF (10 ,Mg/kg) was then assessed by using Monastral blue pigment as an intravascular tracer. The role of NEP and ACE activities in the changes produced by dexamethasone was investigated by examining the effect of the selective inhibitors of these enzymes, phosphoramidon and captopril. Dexamethasone reduced the substance P-induced extravasation by 57% but did not affect the PAF-induced extravasation. The suppressive effect of dexamethasone on substance P-induced extravasation was completely reversed by simultaneously inhibiting NEP and ACE activities, but the inhibition of these enzymes had no effect on PAF-induced extravasation, regardless of whether the rats were pretreated with dexamethasone or not. These results suggest that NEP and ACE mediate a selective inhibitory effect of glucocorticoids on neurogenic plasma extravasation. (J.

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Section: Discussionmentioning

confidence: 95%

“…Glucocorticoids induce the expression of both NEP (10) and ACE (11,12) in cultured cells, and increased degradation oftachykinins by these two enzymes may be a component ofthe antiinflammatory activity ofglucocorticoids.…”

Section: Introductionmentioning

confidence: 99%

Neutral endopeptidase and kininase II mediate glucocorticoid inhibition of neurogenic inflammation in the rat trachea.

Piedimonte¹,

McDonald²,

Nadel³

1991

J. Clin. Invest.

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“…Adrenal steroids regulate multiple components of the renin-angiotensin system, including angiotensinogen (Deschepper & Flaxman 1990, Bunnemann et al 1993, Riftina et al 1995, Ryan et al 1997) and angiotensinconverting enzyme (Mendelsohn et al 1982), both of which could generate more AngII ligand. In addition, the physiological and behavioral actions of AngII can be modulated by mineralocorticoids (Epstein 1982, Fluharty & Epstein 1983, Zhang et al 1984, Wilson et al 1986, King et al 1988 and glucocorticoids (Krakoff et al 1975, Whitworth 1987, Ganesan & Sumners 1989, Sumners et al 1991 at the level of the AT1 receptor (Schiffrin et al 1984, Wilson et al 1986, Sumners & Fregly 1989, Ullian et al 1992.…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid and mineralocorticoid regulation of angiotensin II type 1 receptor binding and inositol triphosphate formation in WB cells

Shelat¹,

Flanagan-Cato²,

Sj³

1999

Journal of Endocrinology

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Mineralocorticoids, glucocorticoids, and angiotensin II (AngII) act cooperatively to maintain body fluid homeostasis. Mineralocorticoids, such as aldosterone and deoxycorticosterone-acetate (DOCA), function synergistically with AngII in the brain to increase salt appetite and blood pressure. In addition, glucocorticoids increase AngII-induced drinking and pressor responses and may also facilitate the actions of aldosterone on salt appetite. The AngII Type 1 (AT1) receptor mediates many of the physiological and behavioral actions of AngII. This receptor is coupled to the G-protein Gq, which mediates AngII-induced inositol triphosphate (IP3) formation. The WB cell line, a liver epithelial cell line that expresses the AT1 receptor, was used to examine the cellular basis of glucocorticoid and mineralocorticoid regulation of AT1 function. In this study corticosterone and dexamethasone treatments increased the number of AT1 receptors by activating the glucocorticoid receptor (GR). This increase in AT1 binding resulted in enhanced AngII-stimulated IP3 formation. However, only supraphysiological doses of aldosterone or DOCA increased AT1 binding, and this effect also was mediated by GR activation. Furthermore, despite evidence that mineralocorticoids and glucocorticoids function together to increase AngII-stimulated actions in vivo, aldosterone and dexamethasone did not act synergistically to affect AT1 binding, Gq expression, or IP3 formation. These results indicate that GR activation, and the subsequent increases in AT1 binding and in AngII-stimulated IP3 formation, may represent a cellular mechanism underlying the synergy between adrenal steroids and AngII.

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“…To overcome these limitations, glucocorticoid-eluting stents have been proposed to deliver local antiinflammatory therapy (154-156) using glucocorticoids devoid of affinity for MR, such as dexamethasone and prednisolone (7). However, there remains the risk that GR may induce changes within the vessel which offset any benefit of conventional anti-inflammatory effects, for example by increasing local angiotensin II (157,158) or endothelin-1 (159) generation or by decreasing endothelial nitric oxide generation (160).…”

Section: Recovery From Intravascular Injurymentioning

confidence: 99%

Glucocorticoids and Cardiovascular Disease

Walker¹

2007

European Journal of Endocrinology

466

386

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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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Induction by Glucocorticoids of Angiotensin Converting Enzyme Production from Bovine Endothelial Cells in Culture and Rat Lung In Vivo

Cited by 130 publications

References 30 publications

Neutral endopeptidase and kininase II mediate glucocorticoid inhibition of neurogenic inflammation in the rat trachea.

Neutral endopeptidase and kininase II mediate glucocorticoid inhibition of neurogenic inflammation in the rat trachea.

Glucocorticoid and mineralocorticoid regulation of angiotensin II type 1 receptor binding and inositol triphosphate formation in WB cells

Glucocorticoids and Cardiovascular Disease

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