Why the study?
Does treatment with endothelin or angiotensin II antagonists reduce the proliferation of vascular smooth muscle cells in subtotally nephrectomized rats?
Does treatment with endothelin or angiotensin II antagonists reduce the proliferation of vascular smooth muscle cells in subtotally nephrectomized rats?
In a rat model of uremia, treatment with endothelin receptor antagonists or losartan reduced growth factor-induced vascular smooth muscle cell proliferation in vitro, suggesting a potential mechanism for attenuating atherosclerosis in renal disease.
Supports ET/Ang II mediation of uremic VSMC proliferation; leaves open translation to human CKD atherosclerosis prevention.
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 ET(A) receptor antagonist, an ET(AB) 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-alpha (TNF-alpha) 153.38+/-10.16 vs 122.27+/-1.41%]. Treatment with ET receptor antagonists or losartan attenuated growth factor-stimulated proliferation (PDGF-BB: ET(A) receptor antagonist, 135.71+/-1.08%; ET(AB) 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.
No takes yet. Share an insight, caveat, or question.
Wolf et al. (2004) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: