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.
Peiró
C
C
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, c/Arzobispo Morcillo, 4, 28029, Madrid, Spain.
Vallejo
S
S
Nevado
J
J
Angulo
J
J
Llergo
J L
JL
Cercas
E
E
Rodríguez-Mañas
L
L
Sánchez-Ferrer
C F
CF
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
D000959:Antihypertensive Agents; D000975:Antioxidants; D007004:Hypoglycemic Agents; D010108:Oxyhemoglobins; D017382:Reactive Oxygen Species