Linoleic acid and oleic acid increase the endothelin-1 binding and action in cultured rat aortic smooth muscle cells

An increase in circulating non-esterified fatty acids (NEFA) has been obser ved in patients with poorly controlled diabetes mellitus. To investigate wh ether fatty acids will affect the endothelin-1 (ET-1) receptor and thus con tribute to the acceleration of atherosclerosis in diabetic patients, cultur ed rat aortic smooth muscle cells (SMC) were maintained in media containing higher (similar to those in diabetic patients) concentrations of oleic aci d (OA) or linoleic acid (LA). The ET-1 binding and ET-1-stimulated thymidin e uptake were then examined. We found that cells treated with OA (500 mu mo l/L) or LA (250 mu mol/L) showed a significant increase in ET-1 receptor am ount as demonstrated by Scatchard analysis (Bmax: 7.40 +/- 1.04 v 2.71 +/- 0.54 fmol/mg and 5.00 +/- 1.00 v 3.32 +/- 0.70 fmol/mg, respectively). No c hange in binding affinity was found. Moreover, both the basal and ET-l-stim ulated thymidine uptake were enhanced by treatment with either LA (basal, 1 1,367 +/- 4,117 cpm/mg; LA, 13.933 +/- 4.003 cpm/mg; ET-1 (10(-8)), 16,931 +/- 4,412 cpm/mg; LA +/- ET-1 (10(-8)), 28,855 +/- 5,217 cpm/mg) or OA (bas al, 4,912 +/- 1,193 cpm/mg, OA, 8,027 +/- 1,318 cpm/mg; ET-1 (10(-8)) 9,947 +/- 2,520 cpm/mg; OA + ET 1 (10(-8)), 16,761 +/- 1,740 cpm/mg). This enhan cement in thymidine uptake was associated with an increase in cell number. Because ET-1 and its receptor are involved in atherogenesis, our findings s uggested that increase in circulating NEFA may contribute to the accelerati on of atherosclerosis in diabetic patients. Further studies to confirm its role in the vascular wall are warranted. Copyright (C) 2000 by W.B. Saunder s Company.