High glucose induces ventricular instability and increases vasomotor tone in rats

Aims/hypothesis. To investigate cardiac repolarization time in streptozotoc in-induced diabetic rats and isolated hearts perfused with high glucose con centration. Methods. We studied the effects of streptozotocin-induced diabe tes on the cardiac repolarisation time (Q-T interval) in Sprague-Dawley rat s 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 n on-diabetic rats, in condition of high glucose concentration. Results. Hype rglycaemia in streptozotocin rats increased mean blood pressure and led to a significant (p < 0.001) prolongation of Q-T values, which normalized afte r 4 days of normoglycaemia with intravenous insulin infusion. Perfusion of isolated hearts in condition of high glucose concentration caused a signifi cant prolongation of Q-T values and increased coronary perfusion pressure ( p < 0.001). The effects of high glucose were completely prevented by glutat hione 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 simila r to those induced by high glucose (p < 0.001). Verapamil completely preven ted Q-T lengthening and reduced by about two-thirds CPP values (p < 0.001). Conclusion/Interpretation. Streptozotocin-diabetes in rats produces signifi cant haemodynamic and electric perturbations that are reversed by normoglyc aemia, 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 nitr ic oxide availability to target cells inducing a state of increased vasomot or tone and ventricular instability.