부산대학교 도서관

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. [ABSTRACT FROM AUTHOR]