The direct effects of streptozotocin and alloxan on contractile function in rat heart

• Published in: Pharmacological research 2009-04, Vol.59 (4), p.235-241
• Main Authors: Salem, K.A., Kosanovic, M., Qureshi, A., Ljubisavljevic, M., Howarth, F.C.
• Format: Article
• Language: English
• Subjects: Action potential; Action Potentials - drug effects; Alloxan; Alloxan - pharmacology; Animals; Contraction; Depression, Chemical; Diabetes; Heart Ventricles - drug effects; Hydrogen-Ion Concentration; In Vitro Techniques; Male; Muscle Cells - drug effects; Myocardial Contraction - drug effects; Myocyte; Rats; Rats, Wistar; Streptozocin - pharmacology; Streptozotocin; Temperature; Time Factors; Ventricular myocytes
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2009.01.003

Streptozotocin (STZ) and alloxan (ALX) are widely used to induce diabetes mellitus in experimental animals. The direct effects of STZ and ALX on the amplitude and time course of ventricular myocyte shortening and on cardiac action potentials were investigated. STZ and ALX (10 −5 M) were dissolved in normal Tyrode (NT), maintained at pH 7.4 and 37 °C and stored for either 15 or 60–120 min. Both compounds reduced the amplitude of myocyte shortening. Compared to NT the amplitude of shortening was 34.7 ± 5.0% and 35.2 ± 6.8% with STZ and 41.0 ± 5.5% and 37.3 ± 5.7% with ALX stored for 15 and 60–120 min, respectively. During a 10 min NT washout STZ myocytes recovered to 56.2 ± 8.3% and 60.5 ± 8.2% and ALX myocytes recovered to 88.9 ± 10.0% and 83.7 ± 9.9% after storage of compounds for 15 and 60–120 min, respectively. Perfusion of the whole heart with ALX induced bradycardia but had no effects on the duration of action potential repolarization at 50% and 70% from peak action potential. The negative inotropic effects of STZ and ALX were not altered by storage. The results suggest that some of the effects on heart reported in STZ- and ALX-induced diabetes may be partly attributed to direct action of these compounds.