Effects of dobutamine and acetylcholine on perfused hearts isolated from streptozocin-induced diabetic rats

In order to study the responsiveness of the diabetic heart to autonomic agents, effects of dobutamine (DOB) and acetylcholine (ACh) on perfused hearts isolated from streptozocin (streptozotocin, STZ)-induced diabetic rats and insulin-treated diabetic rats were evaluated. Male Sprague-Dawley rats, weighing 180-210 g, were divided into control (C) group, diabetes mellitus (DM) group, and diabetes mellitus treated with insulin (DMI) group. C group was injected with buffered vehicle. DM and DMI groups were injected intravenously with 60 mg/kg STZ at the first day. Three days after STZ injection, DMI group was subsequently treated with 4 U of insulin zinc suspension (lente insulin) subcutaneously every day. At 45 days after injection of STZ, experiments were performed using a Langendorff perfused heart preparation. In the evaluation of effect of ACh, heart rate and myocardial developed tension (T) were measured. In the evaluation of effect of DOB, heart was paced at 300 beats/min and T was measured isometrically. Plasma glucose values (mg/dl) were 116.0 +/- 4.9 in C, 482.3 +/- 30.3 in DM, and 204.6 +/- 34.8 in DMI group, respectively. The order of percent increases in T induced by DOB (10(-8)-3 x 10(-6) g) was C greater than DMI greater than DM. The order of percent decreases in T and heart rate by ACh (10(-7)-3 x 10(-6) g) was C greater than DMI greater than DM. These results suggest that both adrenergic receptor-mediated and cholinergic receptor-mediated cardiac responsiveness are significantly depressed in the diabetic heart.