Beneficial effects of beraprost sodium, a stable prostacyclin analogue, in diabetic cardiomyopathy.
We examined whether beraprost sodium (beraprost), a stable prostacyclin analogue, prevented cardiomyopathy in diabetic rats in vivo. Diabetes was induced by a bolus injection of streptozotocin in rat-tail vein. Four weeks after the induction of diabetes, the animals were treated with beraprost (30 micrograms/kg/day, p.o.) for 4 weeks until they were used for the measurement of hemodynamics, electrocardiogram (ECG), and plasma creatine phosphokinase (CK) activity. Nontreated diabetic rats have lower mean blood pressure, heart rate, left ventricular systolic pressure, and peak positive dP/dt at basal levels compared to age-matched normal rats. All of these changes were not improved in beraprost-treated rats. The left ventricular end-diastolic pressure and ST/R ratio in the ECG were significantly increased in diabetic rats. These parameters were significantly improved by beraprost compared with nontreated diabetic rats. Additionally, beraprost significantly suppressed the elevation of plasma CK activity as compared with that in non-treated diabetic rats. Changes in peak positive dP/dt in response to isoproterenol were attenuated in nontreated diabetic rats as compared with age-matched normal rats and beraprost-treated diabetic rats. These results suggest that beraprost is capable of preventing diabetic cardiomyopathy without affecting hyperglycemic condition.
Ueno
Y
Y
Toray Industries, Inc., Basic Research Laboratories, Kanagawa, Japan.
Koike
H
H
Nishio
S
S
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D009202:Cardiomyopathies / Q000517:prevention & control*; D003402:Creatine Kinase / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004562:Electrocardiography / Q000187:drug effects; D011464:Epoprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D016277:Ventricular Function, Left / Q000187:drug effects
D001786:Blood Glucose; D010975:Platelet Aggregation Inhibitors; C048081:beraprost; D013311:Streptozocin; D011464:Epoprostenol; D003402:Creatine Kinase