Cardiovascular and Pulmonary PharmacologyDiabetes-induced down-regulation of β1-adrenoceptor mRNA expression in rat heart
Section snippets
Induction of diabetes
Male Wistar rats, 8 weeks old and 180–200 g in body weight, were assigned, at random, to two groups. The rats were anesthetized lightly with diethyl ether, and the diabetic group received a single injection of streptozotocin (45 mg/kg) in citrate buffer into the tail vein. The control group received an equivalent volume of citrate buffer alone. Control and diabetic rats were caged separately but housed under identical conditions. Both groups of animals were given free access to food and water.
Results
β-Adrenoceptors in membrane fractions derived from ventricular myocardium of control and diabetic rats were identified using [3H]CGP 12177. The specific binding of [3H]CGP 12177 to myocardial membranes was saturable and showed high affinity in both control and diabetic groups (Fig. 1 A). Scatchard analysis of the data revealed that [3H]CGP 12177 bound to a single population of binding sites in both groups (Fig. 1B). The number of β-adrenoceptors was significantly lower in myocardial membranes
Discussion
In accordance with previous studies from this laboratory and others showing a reduction in myocardial β-adrenoceptor density in experimental animals with diabetes 2, 4, 5, 6, 7, the radioligand binding study using [3H]CGP 12177 revealed that the density of β-adrenoceptors was reduced by 50% in ventricular myocardium from rats with 4- to 6-week streptozotocin-induced diabetes. In the present study, we found that this animal model exhibited a significant decrease in the level of myocardial β1
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