Transient elevation of cardiac beta-adrenoceptor responsiveness and receptor number in the streptozotocin-diabetic rat.

1. The effects on cardiac responsiveness of diabetes of up to 12 weeks duration has been examined in streptozotocin-pretreated rats. 2. Two weeks of diabetes resulted in a supersensitivity of isolated left atria and papillary muscles to isoprenaline, which was associated with an increase in the density of ventricular [3H]-dihydroalprenolol binding sites. 3. The beta-adrenoceptor supersensitivity was still evident in both tissues after 4 weeks of diabetes, but in left atria the supersensitivity was reduced compared with that observed at 2 weeks, while for papillary muscles it was greater than at 2 weeks. 4. Following 12 weeks of diabetes, responses of papillary muscles to isoprenaline were similar to controls, while beta-mediated responses of left atria were significantly depressed. 5. The alpha-adrenoceptor-mediated responses of cardiac tissues to phenylephrine were similar to controls following diabetes of 2 or 4 weeks duration. At 12 weeks, however, papillary muscle alpha-adrenoceptor-mediated responses were enhanced. The change in ventricular responsiveness to phenylephrine was not accompanied by any change in [3H]-prazosin binding to ventricular membranes. 6. The results demonstrate a transient elevation of cardiac beta-adrenoceptor sensitivity and receptor density during acute diabetes and illustrate the time- and tissue-dependence of diabetes-induced changes in cardiac adrenoceptor sensitivity.