Mechanisms of enhanced angiotensin II–stimulated signal transduction in vascular smooth muscle by aldosterone

Ullian, Michael E.; Fine, Jana J.

doi:10.1002/jcp.1041610203

Cited by 31 publications

(20 citation statements)

References 30 publications

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“…This group also showed enhanced phospholipase C␥-dependent signaling when VSMCs were preincubated with Ald for 24 hours before Ang II stimulation. 23 In contrast to our findings, transcriptional regulation was involved in the studies by Ullian et al We cannot exclude the possibility that genomic and nongenomic effects might have contributed to our in vivo observations. Nevertheless, the short duration of our in vitro experiments, as well as our results obtained with actinomycin D and cycloheximide, support a nongenomic effect.…”

Section: Mazak Et Al Angiotensin II and Aldosterone 2797contrasting

confidence: 95%

Aldosterone Potentiates Angiotensin II–Induced Signaling in Vascular Smooth Muscle Cells

et al. 2004

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Background-In a double-transgenic human renin and human angiotensinogen rat model, we found that mineralocorticoid receptor (MR) blockade ameliorated angiotensin II (Ang II)-induced renal and cardiac damage. How Ang II and aldosterone (Ald) might interact is ill defined. Methods and Results-We investigated the effects of Ang II (10 Ϫ7 mol/L) and Ald (10 Ϫ7 mol/L) on extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling in vascular smooth muscle cells (VSMCs) with Western blotting and confocal microscopy. Ang II induced ERK 1/2 and JNK phosphorylation by 2 minutes. Ald achieved the same at 10 minutes. Ang IIϩAld had a potentiating effect by 2 minutes. Two oxygen radical scavengers and the epidermal growth factor receptor (EGFR) antagonist AG1478 reduced Ang II-, Ald-, and combination-induced ERK1/2 phosphorylation. Preincubating the cells with the MR blocker spironolactone (10 Ϫ6 mol/L) abolished Ang II-induced ROS generation, EGFR transactivation, and ERK1/2 phosphorylation. Conclusions-Ald potentiates Ang II-induced ERK-1/2 and JNK phosphorylation. Oxygen radicals, the MR, and the EGFR play a role in early signaling induced by Ang II and Ald in VSMCs. These in vitro data may help explain the effects of MR blockade on Ang II-induced end-organ damage in vivo.

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Section: Mazak Et Al Angiotensin II and Aldosterone 2797contrasting

confidence: 95%

Aldosterone Potentiates Angiotensin II–Induced Signaling in Vascular Smooth Muscle Cells

et al. 2004

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“…Aldosterone increases AT1R in rat VSMCs and vessels. 20,21,51 An increasing body of evidence indicates that AT2R exerts antigrowth, antihypertrophic, and pro-apoptotic effects that may counteract the growth stimulation mediated by AT1R. We speculate that the upregulation of AT2R expression by mineralocorticoids could be relevant in the modulation of vascular actions of Ang II.…”

Section: Perspectivesmentioning

confidence: 86%

“…The expression of AT1R appears to be induced by Ang II in vascular smooth muscle, 4 and mineralocorticoids potentiate the action of Ang II in cultured rat vascular smooth muscle cells (VSMCs) by increasing the number of AT1R. 20,21 However, there are few data concerning the physiological regulation of AT2R expression. Dietary sodium depletion, which increases RAAS activity, enhances renal AT2 receptor function 10,22 and expression in both young and mature adult rats, mainly in the glomeruli and interstitial cells.…”

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confidence: 99%

High-Salt Diet Inhibits Expression of Angiotensin Type 2 Receptor in Resistance Arteries

et al. 2005

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Abstract-Recent studies suggested that type 2 angiotensin receptor (AT2R) could contribute to regulation of blood pressure and/or vascular remodeling. A key question relates to the effects of potential modulators of vascular AT2R expression. In the present work, we evaluated if high salt intake (70 mmol/L NaCl in drinking water) could modulate rat mesenteric artery AT2R function and expression. Angiotensin II dose-response curves were studied in rat perfused pressurized small-diameter arteries in the presence of losartan (AT1R antagonist Key Words: mineralocorticoid Ⅲ sodium Ⅲ hypertension Ⅲ vascular remodeling Ⅲ apoptosis T he renin-angiotensin-aldosterone system (RAAS) regulates vascular tone, body fluid volume, electrolyte balance, hormonal secretion, and neuronal activity. The biological effects of angiotensin II (Ang II), the main effector peptide in the vasculature, are mediated by at least 2 receptor isofoms. 1,2 The type 1 receptor (AT1R) mediates vasoconstriction, sympathetic facilitation, and trophic effects. The type 2 receptor (AT2R) is widely expressed during fetal development, whereas in the adult its expression has been detected in many different vessel types, including mesenteric, coronary, and renal arteries. 3-6 AT2R has opposite effects to those of AT1R, ie, it promotes cell apoptosis and inhibits cell proliferation. 6,7 AT2R also attenuates the pressor action of Ang II 8 and mediates vasodilation. 9,10 Recently, it has been shown that Ang II relaxes small mesenteric arteries via AT2R when AT1R are blocked. [11][12][13] Interestingly, the expression of AT2R is increased in several pathologic conditions such as vascular injury, 14 cardiac remodeling, congestive heart failure, and myocardial infarction. 15,16 It has been suggested that in adults the presence of AT2R in vascular tissues may be playing a role in vascular tone and/or tissue remodeling. [17][18][19] Therefore, a key and complex question that arises is how AT1R and AT2R expression are modulated. Several studies indicate interaction between Ang II and aldosterone, affecting the expression of ATRs. The expression of AT1R appears to be induced by Ang II in vascular smooth muscle, 4 and mineralocorticoids potentiate the action of Ang II in cultured rat vascular smooth muscle cells (VSMCs) by increasing the number of AT1R. 20,21 However, there are few data concerning the physiological regulation of AT2R expression. Dietary sodium depletion, which increases RAAS activity, enhances renal AT2 receptor function 10,22 and expression in both young and mature adult rats, mainly in the glomeruli and interstitial cells. 23 Induction of AT2R-mediated modulation of blood pressure was described in rats fed with a synthetic diet, an effect attributed to the stimulation of the RAAS. 8 Bonnet et al 24 have shown that Ang II infusion in the rat induces the expression of AT2R in the mesenteric vasculature. Nevertheless, it is not clear whether Ang II directly mediates the increased AT2R expression or if it is secondary to direct aldosterone action on arte...

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“…1, A and B). Mineralocorticoids upregulate ANG II receptors in VSMCs (211), and signaling of ANG II is amplified by exposure to mineralocorticoids (210,211). Both ANG II and aldosterone stimulate vascular growth and remodeling (82,116,121), perhaps mediated through MAPK and ROS signaling (116,121,155).…”

Section: Mineralocorticoids Cvd and Insulin Actionsmentioning

confidence: 99%

Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance

Cooper

Whaley‐Connell²,

Habibi³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

265

230

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JR. Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance. Am J Physiol Heart Circ Physiol 293: H2009 -H2023, 2007. First published June 22, 2007; doi:10.1152/ajpheart.00522.2007.-Hypertension commonly occurs in conjunction with insulin resistance and other components of the cardiometabolic syndrome. Insulin resistance plays a significant role in the relationship between hypertension, Type 2 diabetes mellitus, chronic kidney disease, and cardiovascular disease. There is accumulating evidence that insulin resistance occurs in cardiovascular and renal tissue as well as in classical metabolic tissues (i.e., skeletal muscle, liver, and adipose tissue). Activation of the renin-angiotensin-aldosterone system and subsequent elevations in angiotensin II and aldosterone, as seen in cardiometabolic syndrome, contribute to altered insulin/ IGF-1 signaling pathways and reactive oxygen species formation to induce endothelial dysfunction and cardiovascular disease. This review examines currently understood mechanisms underlying the development of resistance to the metabolic actions of insulin in cardiovascular as well as skeletal muscle tissue.HYPERTENSION is present in ϳ30% of the adult United States population and often occurs in conjunction with insulin resistance and other components of the cardiometabolic syndrome (CMS) (29,115,163,186,190). According to recent data, up to 70 million Americans have insulin resistance, which plays a significant role in the relationship between hypertension, Type 2 diabetes mellitus, chronic kidney disease (CKD), and cardiovascular (CV) disease (CVD) (69). There is accumulating evidence that insulin resistance occurs in CV and renal tissue as well as in classical metabolic tissues (i.e., skeletal muscle, liver, and adipose tissue) (125,186,190). This review focuses on currently accepted mechanisms underlying the development of resistance to the metabolic actions of insulin in CV tissue (see Figs. 1 and 2) as well as skeletal muscle tissues (27,190) (see Fig. 3). Normal Actions of Insulin in CV TissueBoth insulin and IGF-1 receptors exist in CV tissue (186). Upon binding to specific receptors, they activate a number of downstream signaling systems that result in vasorelaxation (125, 188 -191) and myocardial glucose uptake and alteration of cardiac energy homeostasis (125,186,190). Activation of the insulin receptor (IR) and IGF-1 receptor, ligand-activated transmembrane receptors with tyrosine kinase activity, phosphorylates intracellular substrates including IR substrate (IRS) family members and Shc, which, in turn, serve as docking proteins for downstream signaling molecules (27,125). IRS phosphorylation of tyrosine moieties results in the engagement of Src homology 2 (SH2) domain-binding motifs for SH2 domain signaling molecules, including phosphatidyl 3-kinase (PI3K) and Grb-2. When SH2 domains of the p85 regulatory subunit bind to tyrosine-phosphorylated motifs on IRS-1, this activates the preassociated p110 catalytic subunit to generate phosph...

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Mechanisms of enhanced angiotensin II–stimulated signal transduction in vascular smooth muscle by aldosterone

Cited by 31 publications

References 30 publications

Aldosterone Potentiates Angiotensin II–Induced Signaling in Vascular Smooth Muscle Cells

Aldosterone Potentiates Angiotensin II–Induced Signaling in Vascular Smooth Muscle Cells

High-Salt Diet Inhibits Expression of Angiotensin Type 2 Receptor in Resistance Arteries

Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance

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