Aldosterone, a steroid hormone, has traditionally been viewed as a key regulator of fluid and electrolyte homeostasis, as well as blood pressure, through the activation of mineralocorticoid receptor (MR). However, a number of studies performed in the last decade have revealed an important role of aldosterone/MR in the pathogenesis of renal injury. Aldosterone/MR-induced renal tissue injury is associated with increased renal inflammation and oxidative stress, fibrosis, mesangial cell proliferatio...
Abstract There is increasing evidence demonstrating that the renoprotective effects of mineralocorticoid receptor (MR) blockade are independent of the effects exerted by renin-angiotensin inhibitors. MR is expressed not only in tubular cells but also in other renal cells including glomerular mesangial cells, podocytes, and renal interstitial fibroblasts. Animal experiments have shown that MR blockers prevent aldosterone-induced proteinuria, glomerular injury, and tubulointerstitial fibrosis. In ...
Bone morphogenetic protein (BMP) 4 exerts multiple biological effects on kidney and ureter development. To examine the role of BMP4 in glomerular morphogenesis, we generated transgenic mice with altered BMP4 function in podocytes by conferring tissue-specificity with the nephrin (Nphs1) promoter. At birth, Tg(Nphs1-Nog) mice, which had loss of BMP4 function in podocytes, were found to have glomerular microaneurysms, collapsed glomerular capillary tufts, enlarged Bowman's capsules, and fewer norm...
Aldosterone and angiotensin II (ANG II) contribute to the development and progression of renal damage. Here we investigated the effects of bone morphogenetic proteins (BMPs) on renal cell proliferation evoked by aldosterone and ANG II with mouse mesangial cells, which express mineralocorticoid receptors (MR), ANG II type 1 receptors, and BMP signaling molecules. Aldosterone and ANG II stimulated mesangial cell mitosis and activated ERK1/2 and SAPK/JNK signaling. These aldosterone effects were ne...
Bone morphogenetic proteins play a key role in kidney development and postnatal function. The kidney has been identified as a major site of bone morphogenetic protein (BMP)-7 synthesis during embryonic and postnatal development, which mediates differentiation and maintenance of metanephric mesenchyme. Targeted disruption of BMP-7 gene expression in mice resulted in dysgenic kidneys with hydroureters, causing uremia within 24 h after birth. Several experimental animal models of acute and chronic ...
#1Nancy J. Brown(VUMC: Vanderbilt University Medical Center)H-Index: 80
Purpose of review This review highlights recent clinical studies demonstrating the contribution of aldosterone to cardiovascular mortality, vascular dysfunction, and renal injury in the context of advances in our understanding of the molecular biology of aldosterone. Recent findings Mineralocorticoid receptor antagonism reduces mortality in patients with congestive heart failure and following myocardial infarction. Studies in animal models and in patients with congestive heart failure or hyperte...
We demonstrated recently that chronic administration of aldosterone to rats induces glomerular mesangial injury and activates mitogen-activated protein kinases including extracellular signal-regulated kinases 1/2 (ERK1/2). We also observed that the aldosterone-induced mesangial injury and ERK1/2 activation were prevented by treatment with a selective mineralocorticoid receptor (MR) antagonist, eplerenone, suggesting that the glomerular mesangium is a potential target for injuries induced by aldo...
Aldosterone participates in the pathophysiology of several models of progressive chronic renal disease. Because of the causal connection between transforming growth factor-β1 (TGF-β) and scarring in many such models, we hypothesized that aldosterone could evoke TGF-β in the kidney. Aldosterone infusion for 3 days in otherwise normal rats caused a more than twofold increase in TGF-β excretion without changes in systolic pressure or evidence of kidney damage. Concurrent treatment with amiloride di...
Studies were performed to test the hypothesis that reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK) contribute to the pathogenesis of aldosterone/salt-induced renal injury. Rats were given 1% NaCl to drink and were treated with one of the following combinations for 6 weeks: vehicle (0.5% ethanol, SC, n=6); aldosterone (0.75 μg/H, SC, n=8); aldosterone plus a selective mineralocorticoid receptor antagonist; eplerenone (0.125% in chow, n=8); aldosterone plus an antioxidant...
Last. Ole Skøtt(University of Southern Denmark)H-Index: 39
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Aldosterone has been suggested to elicit vessel contraction via a nongenomic mechanism. We tested this proposal in microdissected, perfused rabbit renal afferent arterioles. Aldosterone had no effect on internal diameter in concentrations from 10−10 to 10−5 mol/L, but aldosterone abolished the ability of 100 mmol/L KCl to induce vascular contraction. The inhibitory effect of aldosterone was observed from 1 pmol/L. The inhibitory effect was significant after 5 minutes and maximal after 20 minutes...
Last. Zhi-Ren Zhang(HMU: Harbin Medical University)H-Index: 16
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In the past, it was believed that the expression of the epithelial sodium channel (ENaC) was restricted to epithelial tissues, such as the distal nephron, airway, sweat glands, and colon, where it is critical for sodium homeostasis. Over the past two decades, this paradigm has shifted due to the finding that ENaC is also expressed in various nonepithelial tissues, notably in vascular endothelial cells. In this review, the recent findings of the expression, regulation, and function of the endothe...
#1Xu Yang(HMU: Harbin Medical University)H-Index: 5
#2Na Niu(HMU: Harbin Medical University)H-Index: 5
Last. Zhi-Ren Zhang(HMU: Harbin Medical University)H-Index: 16
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Previous studies have shown that high salt induces artery stiffness by causing endothelial dysfunction via increased sodium influx. We used our unique split-open artery technique combined with protein biochemistry and in vitro measurement of vascular tone to test a hypothesis that bone morphogenetic protein 4 (BMP4) mediates high salt-induced loss of vascular relaxation by stimulating the epithelial sodium channel (ENaC) in endothelial cells. The data show that high salt intake increased BMP4 bo...
Last. Prasad Konkalmatt(GW: George Washington University)H-Index: 17
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Background The regulation of sodium excretion is important in the pathogenesis of hypertension and salt sensitivity is predictive of cardiovascular events and mortality. C57Bl/6 and BALB/c mice hav...
#2Yoshiro Naito(Hyogo College of Medicine)H-Index: 19
Last. Tohru Masuyama(Hyogo College of Medicine)H-Index: 52
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Excess iron is associated with the pathogenesis of several renal diseases. Aldosterone is reported to have deleterious effects on the kidney, but there have been no reports of the role of iron in aldosterone/salt-induced renal injury. Therefore, we investigated the effects of dietary iron restriction on the development of hypertension and renal injury in aldosterone/salt-induced hypertensive mice. Ten-week-old male C57BL/6J mice were uninephrectomized and infused with aldosterone for four weeks....
Abstract Aldosterone is synthesized in the zona glomerulosa of the adrenal cortex. We previously reported the presence of a functional BMP system including BMP-6 in human adrenocortical cells. BMP-6 contributes to Ang II-induced aldosterone production by activating Smad signaling, in which endogenous BMP-6 action is negatively controlled by Ang II in vitro . In the present study, we examined the in vivo role of BMP-6 in regulation of aldosterone by neutralizing endogenous BMP-6 in rats treated w...
