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 t he ability of drugs with antihypertrophic properties for the vascular wall and/or antioxidant activity, such as captopril, losartan, and nifedipine, o r gliclazide, carvedilol, and ascorbic acid, to interfere with 10 nM glycos ylated 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 inte rval: 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, e specially carvedilol and gliclazide, are particularly effective in preventi ng glycosylated human oxyhaemoglobin-induced vascular smooth muscle cell hy pertrophy. (C) 1999 Elsevier Science B.V. All rights reserved.