title: Pharmacological interference of vascular smooth muscle cell hypertrophy induced by glycosylated human oxyhaemoglobin.
abstract: 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.
authors.affiliation: Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, c/Arzobispo Morcillo, 4, 28029, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Peiró
authors.forename: S
authors.initials: S
authors.lastname: Vallejo
authors.forename: J
authors.initials: J
authors.lastname: Nevado
authors.forename: J
authors.initials: J
authors.lastname: Angulo
authors.forename: J L
authors.initials: JL
authors.lastname: Llergo
authors.forename: E
authors.initials: E
authors.lastname: Cercas
authors.forename: L
authors.initials: L
authors.lastname: Rodríguez-Mañas
authors.forename: C F
authors.initials: CF
authors.lastname: Sánchez-Ferrer
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D006031:Glycosylation; D006801:Humans; D006984:Hypertrophy / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D010108:Oxyhemoglobins / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D000975:Antioxidants; D007004:Hypoglycemic Agents; D010108:Oxyhemoglobins; D017382:Reactive Oxygen Species