Reduced coronary reserve in response to short-term ischaemia and vasoactive drugs in ex vivo hearts from diabetic mice

Aim: The aim of the present study was to compare the coronary flow (CF) reserve of ex vivo perfused hearts from type 2 diabetic (db/db) and non‐diabetic (db/+) mice. Methods: The hearts were perfused in the Langendorff mode with Krebs–Henseleit bicarbonate buffer (37 °C, pH 7.4) containing 11 mmol L^?1 glucose as energy substrate. The coronary reserve was measured in response to three different interventions: (1) administration of nitroprusside (a nitric oxide donor), (2) administration of adenosine and (3) production of reactive hyperaemia by short‐term ischaemia. Results: Basal CF was approximately 15% lower in diabetic when compared with non‐diabetic hearts (2.1 ± 0.1 vs. 2.6 ± 0.2 mL min^?1). The maximum increase in CF rate in response to sodium nitroprusside and adenosine was significantly lower in diabetic (0.6 ± 0.1 and 0.9 ± 0.1 mL min^?1 respectively) than in non‐diabetic hearts (1.2 ± 0.1 and 1.4 ± 0.1 mL min^?1 respectively). Also, there was a clear difference in the rate of return to basal CF following short‐term ischaemia between diabetic and non‐diabetic hearts. Thus, basal tone was restored 1–2 min after the peak hyperaemic response in non‐diabetic hearts, whereas it took approximately 5 min in diabetic hearts. Conclusion: These results show that basal CF, as well as the CF reserve, is impaired in hearts from type 2 diabetic mice. As diabetic and non‐diabetic hearts were exposed to the same (maximum) concentrations of NO or adenosine, it is suggested that the lower coronary reserve in type 2 diabetic hearts is, in part, because of a defect in the intracellular pathways mediating smooth muscle relaxation.