Mineralocorticoids upregulate arterial contraction to epidermal growth factor

Florian, Jennifer A.; Dorrance, Anne M.; Webb, R. Clinton; Watts, Stephanie W.

doi:10.1152/ajpregu.2001.281.3.r878

Cited by 27 publications

(26 citation statements)

References 30 publications

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“…Pharmacological in vivo studies have indicated that mineralocorticoids enhance EGFinduced contraction of arteries (9) and that spironolactone reduces the expression of EGFR mRNA after cerebral ischemia (10). In addition, EGFR expression supports fibrosis in cardiovascular and renal tissue (33−35).…”

Section: Fig 7 Comparison Of Aldosterone Infusion In the Absence Anmentioning

confidence: 99%

“…( 8 ) showed that aldosterone increased the expression of ACE mRNA and that this effect was blocked by the MR antagonist spironolactone in neonatal rat cardiocytes in vitro . In addition, pharmacological in vivo studies have reported that mineralocorticoids enhance epidermal growth factor (EGF)-induced contraction of arteries ( 9 ), and that spironolactone reduces the expression of EGF receptor (EGFR) mRNA after cerebral ischemia ( 10). In addition, Krug et al (11) demonstrated that EGFR is an aldosterone-induced protein and is involved in the manifold pathobiological actions of aldosterone, and also that an interaction between aldosterone and EGFR plays a role in activating the extracellular signalregulated kinases p44ERK and p42ERK.…”

Section: Introductionmentioning

confidence: 99%

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Cardioprotective Mechanisms of Spironolactone Associated with the Angiotensin-Converting Enzyme/Epidermal Growth Factor Receptor/Extracellular Signal-Regulated Kinases, NAD(P)H Oxidase/Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1, and Rho-Kinase Pathways in Aldosterone/Salt-Induced Hypertensive Rats

et al. 2005

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Section: Fig 7 Comparison Of Aldosterone Infusion In the Absence Anmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cardioprotective Mechanisms of Spironolactone Associated with the Angiotensin-Converting Enzyme/Epidermal Growth Factor Receptor/Extracellular Signal-Regulated Kinases, NAD(P)H Oxidase/Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1, and Rho-Kinase Pathways in Aldosterone/Salt-Induced Hypertensive Rats

et al. 2005

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“…12 Increases in EGFR expression and/or activation have been demonstrated after aldo stimulation, ex vivo after the incubation of rat aorta and renal, endothelial, and vascular smooth muscle cultured cells with aldo and in vivo in the aorta of adrenalectomized rats treated with aldo. [13][14][15][16] However, the consequences of EFGR activation to the vascular effects of aldo have not yet been demonstrated in vivo.We hypothesized that EGFR activation might contribute to the damaging effects of aldo in the vasculature in vivo. We analyzed the molecular and functional vascular consequences of Received March 29, 2010; first decision April 19, 2010; accepted September 14, 2010 …”

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confidence: 99%

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confidence: 99%

Epidermal Growth Factor Receptor Mediates the Vascular Dysfunction But Not the Remodeling Induced by Aldosterone/Salt

et al. 2011

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Abstract-Pathophysiological aldosterone (aldo)/mineralocorticoid receptor signaling has a major impact on the cardiovascular system, resulting in hypertension and vascular remodeling. Mineralocorticoids induce endothelial dysfunction, decreasing vasorelaxation in response to acetylcholine and increasing the response to vasoconstrictors. Activation of the epidermal growth factor receptor (EGFR) is thought to mediate the vascular effects of aldo, but this has yet to be demonstrated in vivo. In this study, we analyzed the molecular and functional vascular consequences of aldo-salt challenge in the waved 2 mouse, a genetic model with a partial loss of EGFR tyrosine kinase activity. Deficient EGFR activity is associated with global oxidative stress and endothelial dysfunction. A decrease in EGFR activity did not affect the arterial wall remodeling process induced by aldo-salt. By contrast, normal EGFR activity was required for the aldo-induced enhancement of phenylephrine-and angiotensin II-mediated vasoconstriction. In conclusion, this in vivo study demonstrates that EGFR plays a key role in aldosterone-mediated vascular reactivity. Clinical trials (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study and Randomized Aldactone Evaluation Study) have demonstrated the beneficial effects of administering low doses of pharmacological antagonists of the mineralocorticoid receptor (MR; the receptor of the mineralocorticoid hormone aldosterone [aldo]) to patients with heart failure, with improvements in survival rate and morbidity. 1,2 These clinical benefits may partly result from improved vascular function. 3 The MR is expressed in both endothelium and smooth muscle, 4 and the vessels are now considered to be direct targets of aldo. 5 In the mouse, the 11␤-hydroxysteroid dehydrogenase type II enzyme is expressed in the endothelium but not in the smooth muscle, 4,6 at variance with humans. 7 Therefore, in the mouse, aldo is the specific ligand of the MR in the endothelium but not in the smooth muscle, where glucocorticoids could also activate MR. MR activation affects endothelial function and vascular tone: aldo infusion induces endothelial dysfunction, decreasing vasorelaxation in response to acetylcholine (Ach), and increasing the response to various vasoconstrictors. 5,8,9 We showed recently that an increase in MR signaling in the endothelium is associated with an increase in blood pressure and altered vascular tone. 4 Moreover, patients with primary aldosteronism have a higher aortic wall thickness than those with primary hypertension. 10 Aldo is, thus, recognized as a cardiovascular risk factor that exacerbates vascular injury, 3 although the underlying mechanisms remain unclear.It has been suggested that the epidermal growth factor receptor (EGFR) could play a key role in the cardiovascular effects of aldo. 11 In cultured cells, downstream EGFR signaling cascades are induced by aldo or prevented by MR blockade on aldo stimulation. 12 Increases in EGFR expression and/or activation have...

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“…One important peptide signaling "system" with respect to aldosterone is the epidermal growth factor (EGF) and its receptor (EGFR) (17,18). Pharmacological in vivo studies have shown that mineralocorticoids enhance EGF-induced contraction of arteries (19) and that the MR-antagonist spironolactone reduces the expression of EGFR-mRNA after cerebral ischemia (20). Furthermore, EGFR expression supports fibrosis in cardiovascular and renal tissue (21)(22)(23).…”

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confidence: 99%

Aldosterone Stimulates Epidermal Growth Factor Receptor Expression

Krug

Großmann

Schuster

et al. 2003

Journal of Biological Chemistry

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Mineralocorticoids upregulate arterial contraction to epidermal growth factor

Cited by 27 publications

References 30 publications

Epidermal Growth Factor Receptor Mediates the Vascular Dysfunction But Not the Remodeling Induced by Aldosterone/Salt

Aldosterone Stimulates Epidermal Growth Factor Receptor Expression

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