Hypertension, Vol 19, 464-474, Copyright © 1992 by American Heart Association
RJ Johnson, CE Alpers, A Yoshimura, D Lombardi, P Pritzl, J Floege and SM Schwartz
Angiotensin II (Ang II)-mediated hypertension induces vascular smooth
muscle cell hypertrophy and hyperplasia in systemic blood vessels, but the
effects of Ang II on the intrinsic cell populations within the kidney have
been less well characterized. We infused Ang II for 14 days into rats by
minipump at doses (200 ng/min) that resulted in moderate hypertension (mean
systolic blood pressure 156-172 mm Hg). Small renal arterial vessels of Ang
II-infused rats demonstrated focal injury with fibrinoid necrosis and
medial hyperplasia, whereas the glomerular capillaries demonstrated only
rare segmental hyalinosis. Proliferation of vascular smooth muscle cells
was pronounced (fourfold to 20-fold increase in [3H]thymidine
incorporation) as opposed to a minimal proliferation of glomerular cells in
Ang II-infused rats. In contrast, the principal effect of Ang II in
glomeruli was to increase the expression of alpha-smooth muscle actin by
mesangial cells and desmin by visceral glomerular epithelial cells. Ang
II-infused rats also developed focal tubulointerstitial injury, with
tubular atrophy and dilation, cast formation, an interstitial monocytic
infiltrate, and mild interstitial fibrosis with increased type IV collagen
deposition. The injury was associated with a proliferation of distal
tubule, collecting duct, and interstitial cells as determined by
immunostaining for proliferating cell nuclear antigen, and was accompanied
by an increase in platelet-derived growth factor B-chain messenger RNA in
the area of interstitial injury as localized by in situ hybridization.
Renal interstitial cells also underwent phenotypic modulation in which they
expressed alpha-smooth muscle actin. Vehicle-infused control rats displayed
no tubular injury, proliferation, or phenotypic modulation. Thus, Ang II in
doses that cause moderate hypertension induces marked vascular, glomerular,
and tubulointerstitial injury with cell proliferation, leukocyte
recruitment, phenotypic modulation with the upregulation of proteins
normally associated with smooth muscle cells, and interstitial fibrosis.
ARTICLES
Renal injury from angiotensin II-mediated hypertension
Department of Medicine, University of Washington, Seattle 98195.
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R. J. Johnson, K. L. Gordon, S. Suga, A. M. Duijvestijn, K. Griffin, and A. Bidani Renal Injury and Salt-Sensitive Hypertension After Exposure to Catecholamines Hypertension, July 1, 1999; 34(1): 151 - 159. [Abstract] [Full Text] [PDF]
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M. ABBATE, C. ZOJA, D. ROTTOLI, D. CORNA, N. PERICO, T. BERTANI, and G. REMUZZI Antiproteinuric Therapy while Preventing the Abnormal Protein Traffic in Proximal Tubule Abrogates Protein- and Complement-Dependent Interstitial Inflammation in Experimental Renal Disease J. Am. Soc. Nephrol., April 1, 1999; 10(4): 804 - 813. [Abstract] [Full Text]
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D. Lombardi, K. L. Gordon, P. Polinsky, S. Suga, S. M. Schwartz, and R. J. Johnson Salt-Sensitive Hypertension Develops After Short-Term Exposure to Angiotensin II Hypertension, April 1, 1999; 33(4): 1013 - 1019. [Abstract] [Full Text] [PDF]
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D. P. Healy and L. Song Kidney Aminopeptidase A and Hypertension, Part I : Spontaneously Hypertensive Rats Hypertension, February 1, 1999; 33(2): 740 - 745. [Abstract] [Full Text] [PDF]
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L. Song and D. P. Healy Kidney Aminopeptidase A and Hypertension, Part II : Effects of Angiotensin II Hypertension, February 1, 1999; 33(2): 746 - 752. [Abstract] [Full Text] [PDF]
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E. M. A. Mervaala, D. N. Muller, J.-K. Park, F. Schmidt, M. Lohn, V. Breu, D. Dragun, D. Ganten, H. Haller, and F. C. Luft Monocyte Infiltration and Adhesion Molecules in a Rat Model of High Human Renin Hypertension Hypertension, January 1, 1999; 33(1): 389 - 395. [Abstract] [Full Text] [PDF]
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G. Remuzzi and T. Bertani Pathophysiology of Progressive Nephropathies N. Engl. J. Med., November 12, 1998; 339(20): 1448 - 1456. [Full Text] [PDF]
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P. H. Lane, L. D. Tyler, and P. G. Schmitz Chronic administration of furosemide augments renal weight and glomerular capillary pressure in normal rats Am J Physiol Renal Physiol, August 1, 1998; 275(2): F230 - F234. [Abstract] [Full Text] [PDF]
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 M. Ruiz-Ortega, C. Bustos, M. A. Hernandez-Presa, O. Lorenzo, J. J. Plaza, and J. Egido Angiotensin II Participates in Mononuclear Cell Recruitment in Experimental Immune Complex Nephritis Through Nuclear Factor-{kappa}B Activation and Monocyte Chemoattractant Protein-1 Synthesis J. Immunol., July 1, 1998; 161(1): 430 - 439. [Abstract] [Full Text] [PDF]
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F. Otsuka, T. Yamauchi, H. Kataoka, Y. Mimura, T. Ogura, and H. Makino Effects of chronic inhibition of ACE and AT1 receptors on glomerular injury in Dahl salt-sensitive rats Am J Physiol Regulatory Integrative Comp Physiol, June 1, 1998; 274(6): R1797 - R1806. [Abstract] [Full Text] [PDF]
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 R. J. Dilley and M. I. Nataatmadja Heparin inhibits mesenteric vascular hypertrophy in angiotensin II-infusion hypertension in rats Cardiovasc Res, April 1, 1998; 38(1): 247 - 255. [Abstract] [Full Text] [PDF]
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A. Herizi, B. Jover, N. Bouriquet, and A. Mimran Prevention of the Cardiovascular and Renal Effects of Angiotensin II by Endothelin Blockade Hypertension, January 1, 1998; 31(1): 10 - 14. [Abstract] [Full Text] [PDF]
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K. T. Weber Extracellular Matrix Remodeling in Heart Failure : A Role for De Novo Angiotensin II Generation Circulation, December 2, 1997; 96(11): 4065 - 4082. [Full Text]
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D. Casellas, N. Bouriquet, and A. Herizi Bosentan Prevents Preglomerular Alterations During Angiotensin II Hypertension Hypertension, December 1, 1997; 30(6): 1613 - 1620. [Abstract] [Full Text]
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L.-X. Zou, J. D. Imig, A. M. Von Thun, A. Hymel, H. Ono, and L. G. Navar Receptor-Mediated Intrarenal Angiotensin II Augmentation in Angiotensin II–Infused Rats Hypertension, October 1, 1996; 28(4): 669 - 677. [Abstract] [Full Text]
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D. Gomez-Garre, M. Ruiz-Ortega, M. Ortego, R. Largo, M. J. Lopez-Armada, J. J. Plaza, E. Gonzalez, and J. Egido Effects and Interactions of Endothelin-1 and Angiotensin II on Matrix Protein Expression and Synthesis and Mesangial Cell Growth Hypertension, April 1, 1996; 27(4): 885 - 892. [Abstract] [Full Text]
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G. Wolf, F. N. Ziyadeh, G. Zahner, and R. A.K. Stahl Angiotensin II Is Mitogenic for Cultured Rat Glomerular Endothelial Cells Hypertension, April 1, 1996; 27(4): 897 - 905. [Abstract] [Full Text]
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N. Bouriquet, M. Dupont, A. Herizi, A. Mimran, and D. Casellas Preglomerular Sudanophilia in L-NAME Hypertensive Rats : Involvement of Endothelin Hypertension, March 1, 1996; 27(3): 382 - 391. [Abstract] [Full Text]
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A. Hamaguchi, S. Kim, K. Ohta, K. Yagi, T. Yukimura, K. Miura, T. Fukuda, and H. Iwao Transforming Growth Factor-ß1 Expression and Phenotypic Modulation in the Kidney of Hypertensive Rats Hypertension, July 1, 1995; 26(1): 199 - 207. [Abstract] [Full Text]
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Y. Du, A. Yao, D. Guo, T. Inagami, and D. H. Wang Differential Regulation of Angiotensin II Receptor Subtypes in Rat Kidney by Low Dietary Sodium Hypertension, April 1, 1995; 25(4): 872 - 877. [Abstract] [Full Text]
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