Enhanced expression of EGF receptor in a model of salt-sensitive hypertension

Ying, Wei‐Zhong; Sanders, Paul W.

doi:10.1152/ajprenal.00003.2005

Cited by 27 publications

(22 citation statements)

References 40 publications

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“…Histopathological manifestations of chronic renal injury in Dahl SS rats include glomerular hypertrophy, glomerulosclerosis, interstitial inflammation, interstitial fibrosis, tubular atrophy, and the fibromuscular thickening of interstitial arteries (63,86,94,97,106). In accord with several studies in SHRs (6,44,62,91), we demonstrate that FO prevents the development of chronic glomerular, tubulointerstitial, and vascular alterations in SS ϩ HSD rats.…”

Section: Discussionsupporting

confidence: 88%

“…By quantitative analysis of trichrome-and Sirius red-stained slides, we demonstrate that FO significantly reduces interstitial fibrosis. Arteriopathic alterations, characterized by vascular smooth muscle hyperplasia and luminal constriction, are characteristic histopathological features of renovascular hypertension in Dahl SS rats and in SHRs (88,97,101,106). We found that FO reduced vascular fibromuscular hyperplasia in SS ϩ HSD rats, as evidenced by an increased lumen-to-wall thickness ratio of interlobular-sized arteries and arterioles.…”

Section: Discussionmentioning

confidence: 57%

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Signaling pathways modulated by fish oil in salt-sensitive hypertension

Díaz-Encarnación¹,

Warner²,

Gray³

et al. 2008

American Journal of Physiology-Renal Physiology

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Diaz Encarnacion MM, Warner GM, Gray CE, Cheng J, Keryakos HK, Nath KA, Grande JP. Signaling pathways modulated by fish oil in salt-sensitive hypertension. Am J Physiol Renal Physiol 294: F1323-F1335, 2008. First published April 2, 2008 doi:10.1152/ajprenal.00401.2007.-Although many studies have indicated that fish oil (FO) improves cardiovascular risk factors and reduces histopathological manifestations of injury in experimental renal injury models, potential mechanisms underlying this protective effect have not been adequately defined. The objective of this study was to identify potential signaling pathways that confer protection in the Dahl rat model of salt-sensitive hypertension. Male Dahl saltsensitive rats (n ϭ 10/group) were provided with formulated diets containing 8% NaCl, 20% protein, and 25% FO or 25% corn oil (CO) for 28 days. FO reduced blood pressure (Ϫ11% at 4 wk; P Ͻ 0.05), urine protein excretion (Ϫ45% at 4 wk; P Ͻ 0.05), plasma cholesterol and triglyceride levels (Ϫ54%, P Ͻ 0.001; and Ϫ58%, P Ͻ 0.05), and histopathological manifestations of renal injury, including vascular hypertrophy, segmental and global glomerular sclerosis, interstitial fibrosis, and tubular atrophy. Interstitial inflammation was significantly reduced by FO (Ϫ32%; P Ͻ 0.001), as assessed by quantitative analysis of ED1-positive cells in sections of the renal cortex. FO reduced tubulointerstitial proliferative activity, as assessed by Western blot analysis of cortical homogenates for PCNA (Ϫ51%; P Ͻ 0.01) and quantitative analysis of Mib-1-stained sections of the renal cortex (Ϫ42%; P Ͻ 0.001). Decreased proliferative activity was associated with reduced phospho-ERK expression (Ϫ37%; P Ͻ 0.005) and NF-B activation (Ϫ42%; P Ͻ 0.05). FO reduced cyclooxygenase (COX)-2 expression (Ϫ63%; P Ͻ 0.01) and membrane translocation of the NADPH oxidase subunits p47 phox and p67 phox (Ϫ26 and Ϫ34%; P Ͻ 0.05). We propose that FO ameliorates renal injury in Dahl salt-sensitive rats through the inhibition of ERK, decreased NF-B activation, inhibition of COX-2 expression, and decreased NADPH oxidase activation.fibrosis; glomerulosclerosis; docosahexaenoic acid; eicosapentaenoic acid; rat HYPERTENSIVE NEPHROSCLEROSIS is the second most common cause of end-stage renal disease in the United States (98). Over 70% of the 5.6 million individuals in the United States with elevated serum creatinine levels are hypertensive (16). The risk of end-stage renal disease is directly related to the degree of blood pressure elevation. Hypertension, which occurs in as many as 43 million individuals, is clearly a multifactorial disorder resulting from a variety of environmental and genetic factors. Of the environmental factors, excess dietary salt intake appears to be one of the most important (93, 103). Of note, salt sensitivity is an independent cardiovascular risk factor in patients with hypertension (69).Given the prevalence of hypertension, nontoxic, easily tolerated therapeutic agents that complement standard antihypertensive therapy may play a critical ...

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 57%

Signaling pathways modulated by fish oil in salt-sensitive hypertension

Díaz-Encarnación¹,

Warner²,

Gray³

et al. 2008

American Journal of Physiology-Renal Physiology

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“…17 Furthermore, renal cortical expression of the EGF receptor is increased in both prehypertensive and hypertensive SS rats compared with Sprague-Dawley rats. 39 As measured in this study with ELISA assay, EGF concentration in the kidney cortex of SS rats fed a HS diet was significantly lower compared with SS rats on a LS diet or SS.13 BN rats on both diets ( Figure 6). …”

Section: Egf Deficiency In the Renal Cortex Contributes To Saltsensitsupporting

confidence: 49%

Deficiency of Renal Cortical EGF Increases ENaC Activity and Contributes to Salt-Sensitive Hypertension

Pavlov¹,

Levchenko²,

O’Connor³

et al. 2013

Journal of the American Society of Nephrology

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Various stimuli, including hormones and growth factors, modulate epithelial sodium channels (ENaCs), which fine-tune Na + absorption in the kidney. Members of the EGF family are important for maintaining transepithelial Na + transport, but whether EGF influences ENaC, perhaps mediating salt-sensitive hypertension, is not well understood. Here, the ENaC inhibitor benzamil attenuated the development of hypertension in Dahl salt-sensitive rats. Feeding these salt-sensitive rats a high-salt diet led to lower levels of EGF in the kidney cortex and enhanced the expression and activity of ENaC compared with feeding a lowsalt diet. To directly evaluate the role of EGF in the development of hypertension and its effect on ENaC activity, we infused EGF intravenously while continuously monitoring BP of the salt-sensitive rats. Infusion of EGF decreased ENaC activity, prevented the development of hypertension, and attenuated glomerular and renal tubular damage. Taken together, these findings indicate that cortical EGF levels decrease with a high-salt diet in salt-sensitive rats, promoting ENaC-mediated Na + reabsorption in the collecting duct and the development of hypertension. More than 76 million American adults have high BP 1 and the likelihood of developing hypertension significantly increases with age. Nearly 40% of African Americans aged .20 years exhibit hypertension and nearly 70% of these individuals have a form of hypertension that is highly sensitive to salt intake. A reduced ability to maintain sodium homeostasis and normal levels of arterial pressure is a hallmark of all forms of hypertension. 2 In the kidney, discretionary Na + reabsorption in response to endocrine input to the aldosterone-sensitive distal nephron (ASDN) is a determinant of the pressurenatriuresis relationship, which is of fundamental importance in the long-term control of arterial pressure. 2,3 Although sodium transport in ASDN accounts for a small proportion of renal sodium transport (,10%), ENaC activity is the rate-limiting step for this discretionary Na + reabsorption. 4 The Dahl salt-sensitive (SS) rat strain used in this study is a genetic animal model of hypertension and kidney disease that reveals disease traits similar to those observed in humans. This inbred strain exhibits a low-renin, sodium-sensitive form of hypertension that is associated with severe and progressive proteinuria, glomerulosclerosis, and renal interstitial fibrosis. [5][6][7] The EGF and related hormones are multipotent agents [8][9][10][11] involved in regulation of various renal

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“…Also, the renal VSM expression/ activity of EGFR is increased in Dahl-SS rats before the onset and in established HTN. EGFR mediates the fibrogenic and vasoconstricting actions of ANG II and ET-1, and inhibition of EGFR attenuates the HTN caused by ANG II and the renal vascular fibrosis in L-NAME-induced HTN (47,190).…”

Section: Renal Vsm Dysfunction In Htnmentioning

confidence: 99%

Cellular mediators of renal vascular dysfunction in hypertension

Ponnuchamy¹,

Khalil²

2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Ponnuchamy B, Khalil RA. Cellular mediators of renal vascular dysfunction in hypertension. Am J Physiol Regul Integr Comp Physiol 296: R1001-R1018, 2009. First published February 18, 2009 doi:10.1152/ajpregu.90960.2008.-The renal vasculature plays a major role in the regulation of renal blood flow and the ability of the kidney to control the plasma volume and blood pressure. Renal vascular dysfunction is associated with renal vasoconstriction, decreased renal blood flow, and consequent increase in plasma volume and has been demonstrated in several forms of hypertension (HTN), including genetic and salt-sensitive HTN. Several predisposing factors and cellular mediators have been implicated, but the relationship between their actions on the renal vasculature and the consequent effects on renal tubular function in the setting of HTN is not clearly defined. Gene mutations/ defects in an ion channel, a membrane ion transporter, and/or a regulatory enzyme in the nephron and renal vasculature may be a primary cause of renal vascular dysfunction. Environmental risk factors, such as high dietary salt intake, vascular inflammation, and oxidative stress further promote renal vascular dysfunction. Renal endothelial cell dysfunction is manifested as a decrease in the release of vasodilatory mediators, such as nitric oxide, prostacyclin, and hyperpolarizing factors, and/or an increase in vasoconstrictive mediators, such as endothelin, angiotensin II, and thromboxane A 2. Also, an increase in the amount/activity of intracellular Ca 2ϩ concentration, protein kinase C, Rho kinase, and mitogenactivated protein kinase in vascular smooth muscle promotes renal vasoconstriction. Matrix metalloproteinases and their inhibitors could also modify the composition of the extracellular matrix and lead to renal vascular remodeling. Synergistic interactions between the genetic and environmental risk factors on the cellular mediators of renal vascular dysfunction cause persistent renal vasoconstriction, increased renal vascular resistance, and decreased renal blood flow, and, consequently, lead to a disturbance in the renal control mechanisms of water and electrolyte balance, increased plasma volume, and HTN. Targeting the underlying genetic defects, environmental risk factors, and the aberrant renal vascular mediators involved should provide complementary strategies in the management of HTN. blood pressure; dietary salt; oxidative stress; cytokines; kidney; endothelium; vascular smooth muscle; extracellular matrix; matrix metalloproteinases THE ROLE OF THE KIDNEY IN the regulation of sodium and water balance and blood pressure (BP) is well recognized (53,55,128). A decrease in plasma volume and renal blood flow (RBF) stimulates renin release from the juxtaglomerular cells (JGCs) and activates the renin-angiotensin system (RAS). Renin transforms angiotensinogen to angiotensin I (ANG I), and angiotensin-converting enzyme (ACE) transforms ANG I to ANG II. ANG II stimulates the adrenal cortex to release aldosterone (Aldo), which acts on the rena...

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Enhanced expression of EGF receptor in a model of salt-sensitive hypertension

Cited by 27 publications

References 40 publications

Signaling pathways modulated by fish oil in salt-sensitive hypertension

Signaling pathways modulated by fish oil in salt-sensitive hypertension

Deficiency of Renal Cortical EGF Increases ENaC Activity and Contributes to Salt-Sensitive Hypertension

Cellular mediators of renal vascular dysfunction in hypertension

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