title: High glucose induces ventricular instability and increases vasomotor tone in rats.
abstract: OBJECTIVE
  To investigate cardiac repolarization time in streptozotocin-induced diabetic rats and isolated hearts perfused with high glucose concentration.
  
  
  METHODS
  We studied the effects of streptozotocin-induced diabetes on the cardiac repolarisation time (Q-T interval) in Sprague-Dawley rats during a 4-day period of hyperglycaemia and a subsequent 4-day period of normoglycaemia. The Q-T interval was also evaluated in isolated hearts of non-diabetic rats, in condition of high glucose concentration.
  
  
  RESULTS
  Hyperglycaemia in streptozotocin rats increased mean blood pressure and led to a significant (p < 0.001) prolongation of Q-T values, which normalized after 4 days of normoglycaemia with intravenous insulin infusion. Perfusion of isolated hearts in condition of high glucose concentration caused a significant prolongation of Q-T values and increased coronary perfusion pressure (p < 0.001). The effects of high glucose were completely prevented by glutathione and almost completely by L-arginine, the natural precursor of nitric oxide. In a condition of normal glucose, L-NAME, an inhibitor of endogenous nitric oxide synthesis, increased both Q-T and CPP values to levels similar to those induced by high glucose (p < 0.001). Verapamil completely prevented Q-T lengthening and reduced by about two-thirds CPP values (p < 0.001).
  
  
  CONCLUSIONS
  Streptozotocin-diabetes in rats produces significant haemodynamic and electric perturbations that are reversed by normoglycaemia. Moreover, high glucose increases Q-T and CPP values in the isolated hearts of non-diabetic rats. The latter effects are reversed by glutathione and L-arginine, partially reversed by verapamil and mimicked by L-NAME. By increasing the production of free radicals, high glucose could reduce nitric oxide availability to target cells inducing a state of increased vasomotor tone and ventricular instability.
authors.affiliation: Department of Geriatrics and Metabolic Diseases, Second University of Naples, Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: D'Amico
authors.forename: R
authors.initials: R
authors.lastname: Marfella
authors.forename: F
authors.initials: F
authors.lastname: Nappo
authors.forename: C
authors.initials: C
authors.lastname: Di Filippo
authors.forename: L
authors.initials: L
authors.lastname: De Angelis
authors.forename: L
authors.initials: L
authors.lastname: Berrino
authors.forename: F
authors.initials: F
authors.lastname: Rossi
authors.forename: D
authors.initials: D
authors.lastname: Giugliano
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure; D003326:Coronary Circulation; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology; D004562:Electrocardiography; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006339:Heart Rate; D006352:Heart Ventricles / Q000503:physiopathology; D006943:Hyperglycemia / Q000150:complications*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D014666:Vasomotor System / Q000503:physiopathology*
chemical_list: D004791:Enzyme Inhibitors; D001120:Arginine; D019001:Nitric Oxide Synthase; D005978:Glutathione; D019331:NG-Nitroarginine Methyl Ester