Effects of diazoxide on rat isolated atria

Abstract

Background: It is generally accepted that the selective adenosine triphosphate-dependent potassium channel openers (KATP openers) have a dramatic role in the treatment of some cardiovascular disorders. The aim of this study was to investigate the effects of diazoxide, a potent ATP-related potassium channel opener, on spontaneously beating isolated rat atria to achieve more accurate approaches to treat cardiovascular diseases, such as atrial related disorders including atrial arrhythmias.Methods: After induction of anesthesia, we exsected the heart and isolated the atria of 48 male Wistar rats. Later, we recorded the beating and contractile force of the atria by a physiograph. Subsequently, we studied the effects of diazoxide (2 to 100 µg/mL) on beating and contractile force of the isolated atria 5, 10, 15 and 20 minutes after applying the drug onto the atria.Results: Diazoxide administration (2 to 100 µg/mL) showed a significant decrease (7% to 49% depending on concentration) in atrial beatings (P≤0.001) and in contractile force (1.5% to 67% depending on concentration), (P≤0.001). The effects began several minutes after applying the drug onto the tissues.Conclusion: This study revealed that diazoxide has a direct concentration-dependent effect on cardiac performance and leads to reduction in beating rates and contractile force of the heart. This effect seems to be related to the activation of mitochondrial or sarcolemmal KATP channels. Since the inhibitory action of diazoxide on the heart was very remarkable and prompt, this agent may also exhibit antiarrhythmic properties.

Keywords

• atria
• beating heart
• cardiac arrhythmia
• diazoxide
• isolated
• potassium channel