Effects of adrenergic drugs on isolated and perfused hearts of streptozotocin-induced diabetic rats.
To examine the myocardial contractile response of the diabetic heart, effects of isoproterenol (ISO) and norepinephrine (NE) on perfused hearts isolated from streptozotocin (STZ)-induced diabetic rats and insulin-treated diabetic rats were evaluated. Male Sprague-Dawley rats, weighing 200-260 g, were divided into the control (C)-group, diabetes mellitus (DM)-group and diabetes mellitus treated with insulin (DMI)-group. The C group was injected with buffered vehicle. DM and DMI groups were injected intravenously with 60 mg/kg STZ on the first day. Three days after STZ injection, the DMI group was subsequently treated with 4 U of Lente insulin subcutaneously every day. At 45 days after injection of STZ, experiments were performed using a Langendorff perfused heart preparation. The heart was paced at 300 beats/min, and myocardial developed tension (T) was measured isometrically. Plasma glucose values (mg/dl) were 142.4 +/- 8.7 in C, 499.3 +/- 15.6 in DM and 370.6 +/- 27.6 in DMI group. The order of percent increase in T induced by ISO (3 X 10(-9) - 3 X 10(-8) g) was C = DMI much greater than DM, and that by NE (10(-7) - 10(-6) g) was C greater than DMI greater than DM. On the other hand, the percent increase in T induced by CaCl2 (1.1 X 10(-4) - 2.2 X 10(-3) g) and aminophylline (AMI, 0.31 X 10(-3) - 5.00 X 10(-3) g) was not significantly different among three groups. These results indicate that adrenergic receptor-mediated contractile response was significantly depressed in the diabetic heart.
Sunagawa
R
R
Department of Pharmacology, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
Murakami
K
K
Mimura
G
G
Sakanashi
M
M
D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002122:Calcium Chloride / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D066298:In Vitro Techniques; D007328:Insulin / Q000627:therapeutic use*; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013566:Sympathomimetics / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D013566:Sympathomimetics; D000628:Aminophylline; D007545:Isoproterenol; D002122:Calcium Chloride; D009638:Norepinephrine