QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.105.093112v1 316/1/8    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bolbrinker, J. Articles by Kreutz, R. Search for Related Content PubMed PubMed Citation Articles by Bolbrinker, J. Articles by Kreutz, R.

GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Expression and Response to Angiotensin-Converting Enzyme Inhibition of Matrix Metalloproteinases 2 and 9 in Renal Glomerular Damage in Young Transgenic Rats with Renin-Dependent Hypertension

Department of Clinical Pharmacology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Berlin, Germany (J.B., S.M., M.W., R.K.); and Department of Pathology and Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (W.B.W.H.M., H.v.G.)

Extracellular matrix expansion in the glomerular mesangium contributes to the development of glomerulosclerosis and chronic renal disease in arterial hypertension. Transforming growth factor-1 (TGF-1), matrix metalloproteinases (MMPs), and tissue inhibitors of MMPs (TIMPs) are involved in this process. Conflicting data are reported on the effects of angiotensin II (Ang II) and the response to angiotensin-converting enzyme inhibition on MMPs and TIMPs in early stages of hypertensive glomerular damage. We therefore investigated the effects of Ang II-dependent hypertension on MMP-2, MMP-9, TIMP-1, and TIMP-2 in isolated glomeruli of 8-week-old homozygous male rats overexpressing the mouse Ren2 gene [TGR(mRen2)27]. At this age, systolic blood pressure was already significantly elevated in Ren2 compared with Sprague-Dawley (SD) rats (197 ± 38 versus 125 ± 16 mm Hg, p < 0.01). Ren2 exhibited renal damage as determined by increased urinary albumin excretion, focal glomerulosclerosis, mesangial matrix expansion, and -smooth muscle actin deposition. Quantification of mRNA levels in isolated glomeruli by real-time polymerase chain reaction showed a significant increase of TGF-1, a 2.3- and a 2.6-fold increase of MMP-2 and TIMP-1 in Ren2 compared with SD (p < 0.01, respectively) and no strain differences for TIMP-2. In contrast, MMP-9 mRNA expression was markedly suppressed to 10% of control levels in Ren2 (p < 0.01). Early treatment with ramipril completely prevented renal damage in Ren2 and restored mRNA expression of TGF-1, MMP-2, and TIMP-1 to SD control levels. Interestingly, down-regulation of MMP-9 mRNA, protein, and activity was not affected by ramipril, indicating that the protective effect of this compound is not attributable to restoration of MMP-9 in the glomerulus.

Address correspondence to: Dr. Juliane Bolbrinker, Department of Clinical Pharmacology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. E-mail: juliane.bolbrinker{at}charite.de

This article has been cited by other articles:

				C. S. Samuel, T. D. Hewitson, Y. Zhang, and D. J. Kelly Relaxin Ameliorates Fibrosis in Experimental Diabetic Cardiomyopathy Endocrinology, July 1, 2008; 149(7): 3286 - 3293. [Abstract] [Full Text] [PDF]

				E. Rached, D. Hoffmann, K. Blumbach, K. Weber, W. Dekant, and A. Mally Evaluation of Putative Biomarkers of Nephrotoxicity after Exposure to Ochratoxin A In Vivo and In Vitro Toxicol. Sci., June 1, 2008; 103(2): 371 - 381. [Abstract] [Full Text] [PDF]

				B Galvez-Prieto, J Bolbrinker, P Stucchi, A I de las Heras, B Merino, S Arribas, M Ruiz-Gayo, M Huber, M Wehland, R Kreutz, et al. Comparative expression analysis of the renin-angiotensin system components between white and brown perivascular adipose tissue J. Endocrinol., April 1, 2008; 197(1): 55 - 64. [Abstract] [Full Text] [PDF]

				M. J. Socha, M. Manhiani, N. Said, J. D. Imig, and K. Motamed Secreted Protein Acidic and Rich in Cysteine Deficiency Ameliorates Renal Inflammation and Fibrosis in Angiotensin Hypertension Am. J. Pathol., October 1, 2007; 171(4): 1104 - 1112. [Abstract] [Full Text] [PDF]

				M. H. de Borst, S. H. Diks, J. Bolbrinker, M. W. Schellings, M. B. A. van Dalen, M. P. Peppelenbosch, R. Kreutz, Y. M. Pinto, G. Navis, and H. van Goor Profiling of the renal kinome: a novel tool to identify protein kinases involved in angiotensin II-dependent hypertensive renal damage Am J Physiol Renal Physiol, July 1, 2007; 293(1): F428 - F437. [Abstract] [Full Text] [PDF]

				M. L. Graciano, C. R. Mouton, M. E. Patterson, D. M. Seth, J. J. Mullins, and K. D. Mitchell Renal vascular and tubulointerstitial inflammation and proliferation in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent malignant hypertension Am J Physiol Renal Physiol, June 1, 2007; 292(6): F1858 - F1866. [Abstract] [Full Text] [PDF]

				J. M. Catania, G. Chen, and A. R. Parrish Role of matrix metalloproteinases in renal pathophysiologies Am J Physiol Renal Physiol, March 1, 2007; 292(3): F905 - F911. [Abstract] [Full Text] [PDF]