title: Endothelial dysfunction: Possible mechanisms and ways of correction.
abstract: BACKGROUND
  Endothelial function is impaired in atherosclerosis, hypertension, diabetes and aging, and this may be associated with an attenuated ability of endothelial cells to generate nitric oxide (NO).
  
  
  OBJECTIVE
  To evaluate possible alterations in endothelium-dependent relaxation in rat aortic rings, the activity of constitutive NO synthase and endothelial electrical responses to acetylcholine (Ach) in rat aorta, and the effect of one month of treatment with the angiotensin-converting enzyme inhibitor enalapril on endothelial function.
  
  
  METHODS
  Endothelial membrane potential was measured in excised rat aorta using the perforated patch-clamp technique. Enzyme activity was determined by measuring the rate of formation of L-citrulline from L-arginine.
  
  
  RESULTS
  In old rats and rats with experimental diabetes, the relaxation response to Ach and the activity of constitutive NO synthase were significantly depressed compared with control rats, and the endothelial resting membrane potential was significantly depolarized (-32.7+/-0.8 mV and -28.4+/-3.1 mV, respectively) compared with the control rats (-42.9+/-0.6 mV). The membrane potential attained during peak hyper-polarization to Ach in the arteries of diabetic and old rats (-57.6+/-1.1 mV and -55.7+/-2.1 mV, respectively) did not reach the level attained in the arteries of control rats (-63.1+/-0.6 mV). Enalapril treatment restored the relaxation response to Ach and increased the activity of constitutive NO synthase in aortic rings from diabetic and old rats.
  
  
  CONCLUSIONS
  Altered electrical properties of endothelial cells and attenuated NO synthase activity underpin the suppressed relaxation to Ach in aging and experimental diabetes. Enalapril treatment improves endothelium-dependent relaxation and the activity of constitutive NO synthase.
authors.affiliation: AA Bogomoletz Institute of Physiology, Kiev, Ukraine.
authors.forename: Vadim
authors.initials: V
authors.lastname: Sagach
authors.forename: Alexander
authors.initials: A
authors.lastname: Bondarenko
authors.forename: Olga
authors.initials: O
authors.lastname: Bazilyuk
authors.forename: Anatoliy
authors.initials: A
authors.lastname: Kotsuruba