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Increasing evidence has revealed that glibenclamide has a wide range of anti-inflammatory effects. However, it is unclear whether glibenclamide can affect the resting and adenosine triphosphate (ATP)-induced intracellular calcium ([Ca2+]i) handling in Raw 264.7 macrophages. In the present study, [Ca2+]i transient, reactive oxygen species (ROS) and mitochondrial activity were measured by the high-speed TILLvisION digital imaging system using the indicators of Fura 2-am, DCFDA and rhodamine-123, respectively. We found that glibenclamide, pinacidil and other unselective K+ channel blockers had no effect on the resting [Ca2+]i of Raw 264.7 cells. Extracellular ATP (100 µM) induced [Ca2+]i transient elevation independent of extracellular Ca2+. The transient elevation was inhibited by an ROS scavenger (tiron) and mitochondria inhibitor (rotenone). Glibenclamide and 5-hydroxydecanoate (5-HD) also decreased ATP-induced [Ca2+]i transient elevation, but pinacidil and other unselective K+ channel blockers had no effect. Glibenclamide also decreased the peak of [Ca2+]i transient induced by extracellular thapsigargin (Tg, 1 µM). Furthermore, glibenclamide decreased intracellular ROS and mitochondrial activity. When pretreated with tiron and rotenone, glibenclamide could not decrease ATP, and Tg induced maximal [Ca2+]i transient further. We conclude that glibenclamide may inhibit ATP-induced [Ca2+]i transient elevation by blocking mitochondria KATP channels, resulting in decreased ROS generation and mitochondrial activity in Raw 264.7 macrophages.

BackgroundDiabetic cardiomyopathy (DCM) is a common but underestimated cause of heart failure in patients with diabetes. This study investigated the myocardial-protective effects of nicorandil (Nic) on rats with DCM.Material/MethodsA total of forty-seven 180–220 g male Wistar rats were randomly divided into 4 groups: a control group (control, n=8), a DCM group (DCM, n=13), a nicorandil-pretreated DCM group (Nic1, n=13), and a nicorandil-treated DCM group (Nic2, n=13). A rat model of type 2 diabetes was induced by high-fat and high-sugar diet and intraperitoneal injection of streptozotocin (STZ). Nicorandil (3 mg/kg/d) was orally administrated to rats in the Nic1 group starting at week 4. Nicorandil (3 mg/kg/d) was orally administrated only after the induction of diabetes in the Nic2 group. The serum lipoids, plasma glucose, insulin levels, heart weight index, serum creatine kinase (CK), lactate dehydrogenase (LDH) levels, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) were analyzed in all groups.ResultsThe DCM group showed increased heart weight index, serum LDH, CK, and MDA content and decreased serum SOD activity, as compared with the control group (P<0.05). The DCM-induced increases in heart weight index, serum LDH, CK, and MDA content and decrease in serum SOD activity were attenuated in both Nic1 and Nic2 groups (P<0.05). However, there was no significant difference between Nic1 and Nic2 groups (P>0.05).ConclusionsNicorandil has protective effects on cardiac hypertrophy in DCM rats through increased SOD activity and decreased MDA content. Therefore, nicorandil may be a therapeutic method for diabetic patients with DCM.

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