Article tools
Author information
Published in Volume 100, Issue 5 (September 1,1997)
J. Clin. Invest. 100(5): 1047-1058 (1997). doi:10.1172/JCI119615.
Copyright © 1997, The American Society for Clinical Investigation.

Research Article

Angiotensin II stimulates expression of the chemokine RANTES in rat glomerular endothelial cells. Role of the angiotensin type 2 receptor.

G Wolf, F N Ziyadeh, F Thaiss, J Tomaszewski, R J Caron, U Wenzel, G Zahner, U Helmchen and R A Stahl

Department of Medicine, University of Hamburg, D-20246 Hamburg, Germany.

Published September 1, 1997

Glomerular influx of monocytes/macrophages (M/M) occurs in many immune- and non-immune-mediated renal diseases. The mechanisms targeting M/M into the glomerulus are incompletely understood, but may involve stimulated expression of chemokines. We investigated whether angiotensin II (ANG II) induces the chemokine RANTES in cultured glomerular endothelial cells of the rat and in vivo. ANG II stimulated mRNA and protein expression of RANTES in cultured glomerular endothelial cells. The ANG II-induced RANTES protein was chemotactic for human monocytes. Surprisingly, the ANG II-stimulated RANTES expression was transduced by AT2 receptors because the AT2 receptor antagonists PD 123177 and CGP-42112A, but not an AT1 receptor blocker, abolished the induced RANTES synthesis. Intraperitoneal infusion of ANG II (500 ng/h) into naive rats for 4 d significantly stimulated glomerular RANTES mRNA and protein expression compared with solvent-infused controls. Immunohistochemistry revealed induction of RANTES protein mainly in glomerular endothelial cells and small capillaries. Moreover, ANG II- infused animals exhibited an increase in glomerular ED-1- positive cells compared with controls. Oral treatment with PD 123177 (50 mg/liter drinking water) attenuated the glomerular M/M influx without normalizing the slightly elevated systolic blood pressure caused by ANG II infusion, suggesting that the effects on blood pressure and RANTES induction can be separated. We conclude that the vasoactive peptide ANG II may play an important role in glomerular chemotaxis of M/M through local induction of the chemokine RANTES. The observation that the ANG II- mediated induction of RANTES is transduced by AT2 receptors may influence the decision as to which substances might be used for the therapeutic interference with the activity of the renin-angiotensin system.

This article Copyright © 1997, The American Society for Clinical Investigation.

Articles that cite
this article:

RAS meets SLE
R. P. Wuthrich
nedt 24(9):2634. [CrossRef]

Vascular benefits of angiotensin receptor blockers
Adriaan A Voors,
Expert Opin Invest Drugs 16(7):987. [CrossRef]

NF-κB and chemokine-cytokine expression in renal tubulointerstitium in experimental hyperoxaluria. Role of the renin-angiotensin system
Jorge Eduardo Toblli, Gabriel Cao, Gabriel Casas, Inés Stella, Felipe Inserra, Margarita Angerosa
Urol Res 33(5):358. [CrossRef]

Agents in development for the treatment of diabetic nephropathy
Kei Fukami, Mark E Cooper, Josephine M Forbes
Expert Opin Invest Drugs 14(3):279. [CrossRef]

Messenger RNA expression of RANTES in the urinary sediment of patients with lupus nephritis
REBECCA WING-YAN Chan, FERNAND MAC-MOUNE Lai, EDMUND KWOK-MING Li, LAI-SHAN Tam, KAI-MING Chow, PHILIP KAM-TAO Li, CHEUK-CHUN Szeto
Nephrology (Carlton) 11(3):219. [CrossRef]

Human Chymase Expression in a Mice Induces Mild Hypertension with Left Ventricular Hypertrophy
Takafumi Koga, Hidenori Urata, Yukiko Inoue, Takafumi Hoshino, Takehiro Okamoto, Akira Matsunaga, Misao Suzuki, Junichi Miyazaki, Munehito Ideishi, Kikuo Arakawa
Hypertens Res 26(9):759. [CrossRef]

Angiotensin II blockade and low-protein diet produce additive therapeutic effects in experimental glomerulonephritis
Harm Peters, Wayne A Border, Nancy A Noble
Kidney Int 57(4):1493. [CrossRef]

Molecular mechanisms of angiotensin II-induced vascular injury
Marta Ruiz-ortega, Monica Ruperez, Vanesa Esteban, Jesús Egido
Current Science Inc 5(1):73. [CrossRef]

Angiotensin II induces renal oxidant stress in vivo and heme oxygenase-1 in vivo and in vitro
Eric N. Haugen, Anthony J. Croatt, Karl A. Nath
Kidney Int 58(1):144. [CrossRef]

The Rho-kinase pathway regulates angiotensin II-induced renal damage
MÓNICA RupÉrez, ELSA SÁnchez-lÓpez, LUIS MIGUEL Blanco-colio, VANESA Esteban, JUAN RodrÍguez-vita, JUAN JOSÉ Plaza, JESÚS Egido, MARTA Ruiz-ortega
Kidney Int [CrossRef]

Renal and vascular hypertension-induced inflammation: role of angiotensin II
Marta Ruiz-ortega, Vanesa Esteban, M??nica Rup??rez, Elsa S??nchez-l??pez, Juan Rodr??guez-vita, Gisselle Carvajal, Jes??s Egido
15(2):159???166. [CrossRef]

The renin-angiotensin system and the long-term complications of diabetes: pathophysiological and therapeutic considerations
R. E. Gilbert, H. Krum, J. Wilkinson-berka, D. J. Kelly
Diabetic Med 20(8):607. [CrossRef]

Renal expression of angiotensin type 2 (AT2) receptors during kidney damage
Marta Ruiz-ortega, Vanesa Esteban, Yusuke Suzuki, Monica Ruperez, Sergio Mezzano, Leopoldo Ardiles, Pilar Justo, Alberto Ortiz, Jesus Egido
Kidney Int 64(s86):21. [CrossRef]

Effect of simultaneous blockade of AT1 and AT2 receptors on the NFkappaB pathway and renal inflammatory response
Vanesa Esteban, Monica Ruperez, Juan Rodriguez Vita, Elsa Sanchez Lopez, Sergio Mezzano, Juan Jose Plaza, Jesus Egido, Marta Ruiz-ortega
Kidney Int 64(s86):33. [CrossRef]

Leptin stimulates proliferation and TGF-beta expression in renal glomerular endothelial cells: Potential role in glomerulosclerosis 1
Gunter Wolf, Andreas Hamann, Dong Cheol Han, Udo Helmchen, Friedrich Thaiss, Fuad N. Ziyadeh, Rolf A.K. Stahl
Kidney Int 56(3):860. [CrossRef]

Angiotensin II infusion ameliorates the early phase of a mesangioproliferative glomerulonephritis1
Ulrich O. Wenzel, Friedrich Thaiss, Udo Helmchen, Rolf A.K. Stahl, Gunter Wolf
Kidney Int 61(3):1020. [CrossRef]

Angiotensin II activates nuclear transcription factor-kappaB through AT1 and AT2 receptors1
Gunter Wolf, Ulrich Wenzel, Kevin D. Burns, Raymond C. Harris, Rolf A.K. Stahl, Friedrich Thaiss
Kidney Int 61(6):1986. [CrossRef]

Angiotensin II regulates the synthesis of proinflammatory cytokines and chemokines in the kidney
Marta Ruiz-ortega, Monica Ruperez, Oscar Lorenzo, Vanesa Esteban, Julia Blanco, Sergio Mezzano, Jesus Egido
Kidney Int 62(s82):12. [CrossRef]

Angiotensin II, the AT2 receptor, and nuclear factor-kappaB activation
Friedrich C. Luft
Kidney Int 61(6):2272. [CrossRef]

Chemokines and chemokine receptors are involved in the resolution or progression of renal disease
Hans-Joachim Anders, Volker Vielhauer, Detlef Schlondorff
Kidney Int 63(2):401. [CrossRef]

Effect of candesartan cilexetil (TCV-116) in rats with chronic renal failure
Masakuni Noda, Takanori Matsuo, Ryo Fukuda, Masayuki Ohta, Hiroko Nagano, Yumiko Shibouta, Takehiko Naka, Kohei Nishikawa, Yoshimi Imura
Kidney Int 56(3):898. [CrossRef]

Induction of MIF synthesis and secretion by tubular epithelial cells: A novel action of angiotensin II
Edwina K. Rice, Gregory H. Tesch, Zemin Cao, Mark E. Cooper, Christine N. Metz, Richard Bucala, Robert C. Atkins, David J. Nikolic-paterson
Kidney Int 63(4):1265. [CrossRef]

Dual blockade of the renin-angiotensin system versus maximal recommended dose of ACE inhibition in diabetic nephropathy
Peter Jacobsen, Steen Andersen, Kasper Rossing, Berit R. Jensen, Hans-Henrik Parving
Kidney Int 63(5):1874. [CrossRef]

Heparan sulfate proteoglycans in glomerular inflammation
Angelique L.W.M.M. Rops, Johan Van der vlag, Joost F.M. Lensen, Tessa J.M. Wijnhoven, Lambert P.W.J. Van den heuvel, Toin H. Van kuppevelt, Jo H.M. Berden
Kidney Int 65(3):768. [CrossRef]

Combination therapy with ACE inhibitors and angiotensin II receptor blockers to halt progression of chronic renal disease: Pathophysiology and indications
Gunter Wolf, Eberhard Ritz
Kidney Int 67(3):799. [CrossRef]

Angiotensin II stimulates Pax-2 in rat kidney proximal tubular cells: Impact on proliferation and apoptosis
Shao-Ling Zhang, Jun Guo, Babak Moini, Julie R. Ingelfinger
Kidney Int 66(6):2181. [CrossRef]

Angiotensin III increases MCP-1 and activates NF-kappaB and AP-1 in cultured mesangial and mononuclear cells
Marta Ruiz-ortega, Oscar Lorenzo, Jesus Egido
Kidney Int 57(6):2285. [CrossRef]

F2-isoprostanes mediate high glucose-induced TGF-beta synthesis and glomerular proteinuria in experimental type I diabetes
Angel Montero, Karen A. Munger, Rizwan Z. Khan, Jose M. Valdivielso, Jason D. Morrow, Antonio Guasch, Fuad N. Ziyadeh, Kamal F. Badr
Kidney Int 58(5):1963. [CrossRef]

Monocyte chemoattractant protein-1 and macrophage infiltration in hypertensive kidney injury
Karl F. Hilgers, Andrea Hartner, Markus Porst, Monika Mai, Michael Wittmann, Christian Hugo, Detlev Ganten, Helmut Geiger, Roland Veelken, Johannes F.E. Mann
Kidney Int 58(6):2408. [CrossRef]

Angiotensin type 2 receptor is expressed in the adult rat kidney and promotes cellular proliferation and apoptosis
Zemin Cao, Darren J. Kelly, Alison Cox, David Casley, Josephine M. Forbes, Paul Martinello, Rachael Dean, Richard E. Gilbert, Mark E. Cooper
Kidney Int 58(6):2437. [CrossRef]

An extremely high dose of losartan affords superior renoprotection in the remnant model
Clarice Kazue Fujihara, Mariliza Velho, Denise Maria Avancini costa malheiros, Roberto Zatz
Kidney Int 67(5):1913. [CrossRef]

Nephroprotection by antifibrotic and anti-inflammatory effects of the vasopeptidase inhibitor AVE7688
OLIVER Gross, MARIE-LOUISE Koepke, BOGDAN Beirowski, ECKHARD Schulze-lohoff, STEPHAN Segerer, MANFRED Weber
Kidney Int 68(2):456. [CrossRef]


Marta Ruiz-ortega, Oscar Lorenzo, Yusuke Suzuki, Monica Ruperez, Jesus Egido
Curr Opin Nephrol Hypertens 10(3):321. [CrossRef]


Fabrice Bonnet, Riccardo Candido, Robert Carey, David Casley, Leileata Russo, Tanya Osicka, Mark Cooper, Zemin Cao
J Hypertens 20(8):1615. [CrossRef]

Peroxisome proliferator-activated receptors ligands and ischemia-reperfusion injury
Rosanna Paola, Salvatore Cuzzocrea
naunyn-schmiedeberg&apos s arch pharmacol 375(3):157. [CrossRef]

Angiotensin receptors: beyond number one
Agnes B Fogo
13(3):275. [CrossRef]

Chemokines and nephritis
Rolf A. K. Stahl
Clin Exp Nephrol 2(4):264. [CrossRef]

Das Renin-Angiotensin-Aldosteron-System als Zentraler Mediator der Progression der Niereninsuffizienz
K. A. Pöschel, G. Wolf
Nephrologe 1(4):233. [CrossRef]

Optimal strategies for preventing progression of renal disease: Should angiotensin converting enzyme inhibitors and angiotensin receptor blockers be used together?
Radko Komers, Sharon Anderson
Current Science Inc 2(5):465. [CrossRef]

Clinical trials report
Norman M. Kaplan, Donald G. Vidt
Current Science Inc 6(5):339. [CrossRef]

Angiotensin II and the glomerulus: Focus on diabetic kidney disease
James W. Scholey
Current Science Inc 5(2):172. [CrossRef]

Renal effects of dual renin–angiotensin–aldosterone system blockade in patients with diabetic nephropathy
M. Dalla vestra, N. Simioni, A. Masiero
Int Urol Nephrol 41(1):119. [CrossRef]

Modulation of glomerulosclerosis
Li-Jun Ma, Agnes B. Fogo
Semin Immunopathol 29(4):385. [CrossRef]

Angiotensin II type 2 receptor deficiency aggravates renal injury and reduces survival in chronic kidney disease in mice
Ralf A Benndorf, Christian Krebs, Birgit Hirsch-hoffmann, Edzard Schwedhelm, Gabriele Cieslar, Robin Schmidt-haupt, Oliver M Steinmetz, Catherine Meyer-schwesinger, Friedrich Thaiss, Munif Haddad
Kidney Int 75(10):1039. [CrossRef]

Human mast cell chymase induces the accumulation of neutrophils, eosinophils and other inflammatory cells in vivo
Shaoheng He, Andrew F. Walls
Br J Pharmacol 125(7):1491. [CrossRef]

Glomerular type 1 angiotensin receptors augment kidney injury and inflammation in murine autoimmune nephritis
Steven D. Crowley, Matthew P. Vasievich, Phillip Ruiz, Samantha K. Gould, Kelly K. Parsons, A. Kathy Pazmino, Carie Facemire, Benny J. Chen, Hyung-Suk Kim, Trinh T. Tran
J Clin Invest [CrossRef]