Effects of Combined Endothelin and Angiotensin II Antagonism on Growth Factor-Induced Proliferation of Vascular Smooth Muscle Cells Isolated from Uremic Rats

Background. The activation of both the renin–angiotensin–aldosterone and endothelin (ET) system in uremia contributes to the development of cardiovascular disease. The combination of ET receptor antagonists and inhibitors of the angiotensin-converting enzyme (ACE) or angiotensin II type 1 (AT1) receptor could therefore inhibit atherogenesis. We studied the effects of different medications on growth-factor-induced proliferation of vascular smooth muscle cells (VSMC) isolated from uremic rats. Methods. Subtotally nephrectomized rats (SNX) were treated with an ETA receptor antagonist, losartan, trandolapril, or the combinations of an ETA receptor antagonist and losartan or trandolapril for 12 weeks. Proliferation induced by different growth factors in isolated aortal SMC was measured using a BrdU-ELISA. Results. Maximum proliferation in response to PDGF-BB, bFGF, and TNF-α which was higher in untreated SNX than in controls (PDGF-BB: 486.60 ± 8.27% versus 346.74 ± 4.60%, n = 8), was reduced after monotherapy ...