Pharmacological interference of vascular smooth muscle cell hypertrophy induced by glycosylated human oxyhaemoglobin

Nonenzymatically glycosylated human oxyhaemoglobin induces vascular smooth muscle cell hypertrophy by releasing reactive oxygen species. We analysed the ability of drugs with antihypertrophic properties for the vascular wall and/or antioxidant activity, such as captopril, losartan, and nifedipine, or gliclazide, carvedilol, and ascorbic acid, to interfere with 10 nM glycosylated human oxyhaemoglobin-induced increase in vascular smooth muscle cell size (118 +/- 0.5% of basal). Vascular smooth muscle cell hypertrophy was abolished concentration-dependently, with pD(2) values over a 100-fold interval: 6.4 +/- 0.3, 7.7 +/- 0.4, 7.3 +/- 0.4, 7.4 +/- 0.6, 8.8 +/- 0.2, and 9.0 +/- 0.2 for captopril, losartan, nifedipine, ascorbic acid, carvedilol and gliclazide, respectively. Drugs with powerful antioxidant properties, especially carvedilol and gliclazide, are particularly effective in preventing glycosylated human oxyhaemoglobin-induced vascular smooth muscle cell hypertrophy. (C) 1999 Elsevier Science B.V. All rights reserved.