Diabetes mellitus is frequently associated with cardiovascular autonomic neuropathy that represents a serious complication of diabetes and seems to be an important factor related to the development of diabetic cardiomyopathy. The purpose of this study was to evaluate how diabetes affects the content of noradrenaline (NA) in the heart atria in early and later stages of streptozotocin (STZ; 65 mg/kg, i.v.)-induced diabetes in female rats, i.e. 1, 4 and 20 months after the onset of the disease (STZ1, STZ4 and STZ20, respectively). In addition, carrier-mediated release of NA from the sliced atria superfused with oxygenated Krebs-Henseleit solution was studied in vitro in the presence or absence of tyramine. Chronotropic effect of tyramine was evaluated on the isolated spontaneously beating right atria (n=6 per group). NA concentrations in the superfusates and tissue extracts were measured by radioimmunoassay. All animals were humanely killed at the end of the experiments and all procedures were performed according to current EU legislation. Statistical analysis was performed using one-way ANOVA (P<0.05) and post hoc Student’s unpaired t test with Bonferroni correction. Data are presented as mean±S.E.M. The diabetic state significantly affected NA concentrations in the heart atria. An initial significant increase in STZ1 atria (n=7; P<0.05 vs controls) was followed by a sustained decline in tissue NA concentrations that became significantly different in STZ20 atria (n=6; P<0.05 vs controls). In the control right atria, the spontaneous beating rate was 223±6 min^-1 and it did not change significantly with age. Tyramine increased the heart rate in a concentration-dependent manner (30% over basal values in the concentration 0.1 mmol/l) and its effect was comparable in all age groups. In contrast, diabetic STZ1 and STZ4 atria had significantly lower spontaneous beating rate (140±9 min^-1; P<0.05 vs controls). Tyramine increased the beating rate by 30% in STZ1 and STZ4 samples and by 110% in STZ20 atria, i.e. significantly more than in the age-matched controls (P<0.01). Basal release of NA from the control atria of all age groups was 0.44±0.2 ng/g/min (n=6 per group) and tyramine (1μmol/l) increased the NA output by 300%. In the diabetic preparations (n=6 per group), tyramine effect varied in relation to the disease duration: In STZ1 atria, the effect of tyramine was similar as in the age-matched controls despite increased atrial NA concentration in the diabetic group. In STZ4 atria, tyramine enhanced NA outflow to a lesser extent than in controls and in STZ20 diabetic samples, tyramine-induced release was by 270% greater than in the control preparations (P<0.01). In conclusion, STZ-induced chronic diabetic state seemed to lead to the cardiac sympathetic denervation as evidenced by decreasing atrial concentrations of NA in the course of the disease. However, this quantitative defect might be at least partly compensated by the increased release of NA from the remaining sympathetic fibres.