Journal Article

Influence of growth factors on the proliferation of vascular smooth muscle cells isolated from subtotally nephrectomized rats after endothelin or angiotensin II antagonism

Sabine C. Wolf, Gabriele Sauter, Hans-Peter Rodemann, Teut Risler and Bernhard R. Brehm

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 20, issue 2, pages 312-318
Published in print February 2005 | ISSN: 0931-0509
Published online December 2004 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfh606
Influence of growth factors on the proliferation of vascular smooth muscle cells isolated from subtotally nephrectomized rats after endothelin or angiotensin II antagonism

Show Summary Details

Preview

Background. Cardiovascular disease is the most important cause of death in patients with end-stage renal disease. In uraemia, the renin–angiotensin–aldosterone and endothelin (ET) systems are activated. It is not known whether inhibition of these systems attenuates the proliferation of isolated smooth muscle cells of uraemic rats.

Methods. Subtotally nephrectomized (SNX) rats were treated with an ETA receptor antagonist, an ETAB receptor antagonist, the angiotensin type 1 (AT1) receptor antagonist losartan (all 10 mg/kg body weight/day) or the angiotensin-converting enzyme (ACE) inhibitor trandolapril (0.1 mg/kg body weight/day) or received no medication (SNX) for 12 weeks. Then, aortal smooth muscle cells (SMCs) were isolated and cultivated. After incubation of SMCs with different growth factors (5–7 days), proliferation was measured using a bromodeoxyuridine enzyme-linked immunosorbent assay (BrdU ELISA).

Results. Higher maximum levels of proliferation were found in SMCs from untreated SNX rats than in SMCs from control animals [platelet-derived growth factor-BB (PDGF-BB) 486.60±8.27 vs 346.74±4.60%, basic fibroblast growth factor (bFGF) 176.68±6.50 vs 123.71±1.49%, tumour necrosis factor-α (TNF-α) 153.38±10.16 vs 122.27±1.41%]. Treatment with ET receptor antagonists or losartan attenuated growth factor-stimulated proliferation (PDGF-BB: ETA receptor antagonist, 135.71±1.08%; ETAB receptor antagonist, 122.72±0.58%; losartan: 103.69±1.83%, n = 8). SMCs from trandolapril-treated rats showed an increased response (PDGF-BB 663.48±7.00%, n = 8).

Conclusions. Treatment of SNX rats with ET receptor antagonists or losartan reduced growth factor-induced SMC proliferation in vitro. However, further investigations with uraemic patients have to clarify whether angiotensin or ET receptor antagonists inhibit the development of atherosclerosis.

Keywords: growth factors; proliferation; SMC; uraemia

Journal Article.  4361 words.  Illustrated.

Subjects: Nephrology

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.