Background: 

Patients with established heart failure and elevated HbA1c display an unexpected improved survival compared to patients with similar symptoms of heart failure but normal HbA1c. Hearts isolated from animals exposed to streptozotocin (an experimental model of diabetes) display improved ß-adrenoceptor responsiveness. These data suggest an improved coupling of ß-adrenoceptor in hyperglycaemia. The present study was aimed to analyze ß-adrenoceptor responsiveness in the absence/presence of hyperglycaemia.

Methods: 

Isolated adult rat ventricular cardiomyocytes were cultured under normoglycaemic or hyperglycaemic conditions for 24 h. Thereafter, cell shortening of cardiomyocytes in the presence of isoprenaline was determined.

Results: 

Hyperglycaemic cardiomyocytes display an improved ß-adrenoceptor responsiveness (+9.41.1%, p<0.001, n=43 cells). The response to isoprenaline was completely attenuated by either atenolol or metoprolol indicating that ß-adrenoceptor antagonists are still working. The maximal calcium-induced cell shortening, however, was not improved. Normalization of glucose levels during the isoprenaline test pulse did not attenuate the improved ß-adrenoceptor stimulation. It was speculated that either reactive oxygen species or nitric oxide are mediated by the hyperglycaemic-induced ß-adrenoceptor responsiveness. Therefore, vitamin C and L-nitro arginine (L-NA) were used to attenuate the effect of hyperglycaemia on ß-adrenoceptor responsiveness. While vitamin C had no effect at all, L-NA totally attenuated the effect of hyperglycaemia on ß-adrenoceptor responsiveness. Angiotensin II that was sufficient to reduce basal cell shortening did not attenuate the effect of hyperglycaemia. However, TGF-ß1 that induces a heterologeous desentization of ß-adrenoceptors attenuated a hypersensibilization of ß-adrenoceptors by hyperglycaemia.

Conclusion: 

Hyperglycaemia induces a hypersensibilization of ß-adrenoceptors in a NO-dependent way that is sufficient to antagonize angiotensin II-dependent effects on cardiac function in the early phase of heart failure.