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

Eur J Pharmacol. 1999 Dec 15;386(2-3):317-21. doi: 10.1016/s0014-2999(99)00781-5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology
  • Antioxidants / pharmacology*
  • Cells, Cultured
  • Glycosylation
  • Humans
  • Hypertrophy / chemically induced
  • Hypoglycemic Agents / pharmacology
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / pathology
  • Oxyhemoglobins / adverse effects
  • Oxyhemoglobins / antagonists & inhibitors*
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism

Substances

  • Antihypertensive Agents
  • Antioxidants
  • Hypoglycemic Agents
  • Oxyhemoglobins
  • Reactive Oxygen Species