Angiotensin II regulates the synthesis of proinflammatory cytokines and chemokines in the kidney

Ruíz-Ortega, Marta; Rupérez, Mónica; Lorenzo, Óscar; Esteban, Vanesa; Blanco, Julia; Mezzano, Sergio; Egido, Jesús

doi:10.1046/j.1523-1755.62.s82.4.x

Cited by 366 publications

(328 citation statements)

References 41 publications

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“…14,15 Studies in hypertensive individuals have shown increased plasma and vascular tissue levels of C-reactive protein (CRP) and several inflammatory cytokines, suggesting a potential association between vascular inflammation and hypertension. [16][17][18][19] Although the evidence for a direct relationship between salt intake and BP is basically established, [20][21][22][23] the clinical evidence is not adequate to consider whether this effect translates into increased incidence of cardiovascular diseases independent from BP in patients with high dietary salt consumption. In this study, we hypothesized that dietary salt intake may be related with inflammation and albuminuria independently from BP in non-diabetic hypertensive patients.…”

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confidence: 99%

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Dietary salt intake is related to inflammation and albuminuria in primary hypertensive patients

et al. 2012

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BACKGROUND/OBJECTIVES:In this study, we hypothesized that dietary salt intake may be related with inflammation and albuminuria independently from blood pressure (BP) in non-diabetic hypertensive patients. SUBJECTS/METHODS: A total of 224 patients with primary hypertension were included in the study. Serum C-reactive protein (CRP) levels, 24-h urine sodium and albumin excretion were measured in all patients. The subjects were divided into tertiles according to the level of 24-h urinary sodium excretion: low-salt-intake group (n ¼ 76, mean urine sodium: 111.7 ± 29.1 mmol/24 h), mediumsalt-intake group (n ¼ 77, mean urine sodium: 166.1 ± 16.3 mmol/24 h) and high-salt-intake group (n ¼ 71, mean urine sodium: 263.6±68.3 mmol/24 h). RESULTS: Systolic and diastolic BP measurements of patients were similar in the three salt-intake groups. CRP and urinary albumin levels were significantly higher in high-salt-intake group compared with medium-and low-salt-intake groups (P ¼ 0.0003 and P ¼ 0.001, respectively). CRP was positively correlated with 24-h urinary sodium excretion (r ¼ 0.28, P ¼ 0.0008) and albuminuria, whereas albuminuria was positively correlated with 24-h urinary sodium excretion (r ¼ 0.21, P ¼ 0.0002). Multiple regression analysis revealed that urinary sodium excretion was an independent predictor of both CRP and albuminuria. CONCLUSIONS: These findings suggest that high salt intake is associated with enhanced inflammation and target organ damage reflected by increased albuminuria in treated hypertensive patients independent of any BP effect. Keywords: albuminuria; hypertension; inflammation; salt intake INTRODUCTION Salt intake is an important factor in the genesis of primary hypertension. Epidemiological and clinical data have showed that high salt intake is associated with increased risk of cardiovascular diseases and stroke. 1 Recent work has provided further evidence that high dietary salt intake may even partly cause blood pressure (BP) -independent target organ damage including left ventricular hypertrophy and microalbuminuria. [2][3][4] Microalbuminuria is a significant predictor of endothelial dysfunction and an independent marker of cardiovascular diseases in patients with primary hypertension. 5,6 Several studies have demonstrated that high salt intake is positively related to urinary albumin excretion and this relation may be independent of BP. 3,4,7 The mechanisms responsible for this effect are unclear. In animal models, dietary salt overload has been demonstrated to contribute to renal injury documented by albuminuria and decreased glomerular filtration rate with a minimally increased arterial pressure. 8,9 Inflammatory mechanisms have been proposed to have a role in this nephrotoxic effect of salt excess. 9-13 The role of inflammation in the initiation and progression of cardiovascular diseases is increasingly recognized. 14,15 Studies in hypertensive individuals have shown increased plasma and vascular tissue levels of C-reactive protein (CRP) and several inflammatory cytokines, suggesting a...

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Dietary salt intake is related to inflammation and albuminuria in primary hypertensive patients

et al. 2012

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“…In kidney and other organs, AngII stimulates expression of proinflammatory mediators, including growth factors, cytokines and chemokines, and adhesion molecules (10,11). Infusion of AngII into rats causes inflammatory cells to invade the glomeruli and interstitium (12)(13)(14). In addition, inflammatory cells can themselves produce AngII, generating a positive feedback loop that perpetuates the inflammatory response and progressive renal injury (15).…”

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Long-Term, High-Dosage Candesartan Suppresses Inflammation and Injury in Chronic Kidney Disease

Chen¹,

Gong²,

Rifai

et al. 2007

Journal of the American Society of Nephrology

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Recent evidence suggests that higher-than-usual antihypertensive dosages of renin-angiotensin-aldosterone system blockers may provide additional protection from progression of chronic renal disease; however, there have been few long-term studies, and the underlying mechanisms remain uncertain. This study examined the effects of long-term (14 mo) administration of ultrahigh dosages of the angiotensin receptor blocker candesartan on the progression of renal injury in spontaneously hypertensive rats (SHR). Beginning 8 wk after birth, SHR underwent unilateral nephrectomy and were given vehicle (control), or candesartan at a standard 5 mg/kg per d (T5), high 25 mg/kg per d (T25), or ultrahigh 75 mg/kg per d dosage (T75). After 2 wk, BP was reduced in all treated groups; however, it was better controlled in the high-dosage groups (T25 and T75). Urinary protein was significantly reduced in T75 after 2 wk of treatment and was also declined in the other two treatment groups but only after 2 mo. Exogenous angiotensin II test showed that complete angiotensin receptor blockade was achieved only in the high-dosage groups. Renal inflammation and macrophage (ED-1) infiltration were significantly ameliorated in both T25 and T75 but not in T5 rats. This was associated with the changes of tubular expression of monocyte chemoattractant protein-1, RANTES (regulated upon expression normal T cell expressed and secreted), and the phosphorylated NF-B, a marker for activation. Suppression of ED-1, monocyte chemoattractant protein-1, and RANTES expression and NF-B activation were greater in T75 as compared with T25. These findings suggest that candesartan has dosage-dependent, anti-inflammatory effects that are mediated by suppression of NF-B activation and chemokine expression. Renal protection with high-dosage therapy may depend on these nonhemodynamic effects.

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“…The diverse effects of angiotensin II on the kidney include 1) promotion of glomerular capillary hypertension due to efferent arteriole vasoconstriction (20,21), 2) stimulation of transforming growth factor-β (TGF-β) production by mesangial cells and tubular epithelial cells (22)(23)(24), 3) stimulation of matrix protein synthesis (23), 4) interstitial fibrosis (25,26), 5) mesangial cell growth (27,28), 6) changes of tubular epithelial cell phenotype and tubulointerstitial cell kinetics (29), 7) cytokine release from renal cells (30), and 8) activation of nuclear factor-κB (NF-κB) and increased monocyte chemoattractant protein-1 (MCP-1) gene expression on mesangial cells, leading to macrophage infiltration (10,31,32). These actions of angiotensin II are known to be the common pathway for several types of renal injury.…”

Section: Discussionmentioning

confidence: 99%

Pathological Regression by Angiotensin II Type 1 Receptor Blockade in Patients with Mesangial Proliferative Glomerulonephritis

et al. 2008

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Angiotensin II regulates the synthesis of proinflammatory cytokines and chemokines in the kidney

Cited by 366 publications

References 41 publications

Dietary salt intake is related to inflammation and albuminuria in primary hypertensive patients

Dietary salt intake is related to inflammation and albuminuria in primary hypertensive patients

Long-Term, High-Dosage Candesartan Suppresses Inflammation and Injury in Chronic Kidney Disease

Pathological Regression by Angiotensin II Type 1 Receptor Blockade in Patients with Mesangial Proliferative Glomerulonephritis

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