Negative regulation of β-adrenergic function by hydrogen sulphide in the rat hearts

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• 作者：Qian Chen Yong ; Ting-Ting Pan ; Li-Fang Hu ; Jin-Song Bian
• 关键词：Hydrogen sulphide ; β ; -Adrenoceptor ; Cardiac myocytes ; cAMP ; Arrhythmias
• 刊名：Journal of Molecular and Cellular Cardiology
• 出版年：2008
• 期刊代码：171_00222828
• 类别：bio
• 出版时间：April 2008
• 卷：44
• 期：4
• 页码：701-710
• 文件大小：1458 K

摘要

β-Adrenoceptor is over-stimulated during myocardial ischemia, in which hydrogen sulphide (H₂S) concentration was found to be lowered. The present study attempted to investigate if H₂S modulates β-adrenoceptor function and the underlying mechanism. We examined the effect of NaHS (a H₂S donor) on myocyte contraction and electrically-induced (EI) intracellular calcium ([Ca²⁺]_i) transients upon β-adrenergic stimulation in rat ventricular myocytes with a video edge tracker method and a spectrofluorometric method using fura-2/AM as a calcium indicator, respectively. We found that isoproterenol (ISO, 10^{− 9}–10^{− 6} M), a β-adrenoceptor agonist, concentration-dependently increased the twitch amplitude of ventricular myocytes, which was attenuated by NaHS (10^{− 5}–10^{− 3} M) in a dose-dependent manner. The amplitudes and maximal velocities (± dl/dt) of myocyte twitch and EI-[Ca²⁺]_i transient amplitudes were enhanced by ISO, forskolin (an adenylyl cyclase activator), 8-bromoadenosine-3′,5′-cyclic monophosphate (an activator of protein kinase A) and Bay K-8644 (a selective L-type Ca²⁺ channel agonist). Administration of NaHS (100 μM) only significantly attenuated the effects of ISO and forskolin. Moreover, NaHS reversed ISO-induced cAMP elevation and forskolin-stimulated adenylyl cyclase activity. In addition, stimulation of β-adrenoceptor by ISO significantly decreased endogenous H₂S production in rat ventricular myocytes. In conclusion, H₂S may negatively modulate β-adrenoceptor function via inhibiting adenylyl cyclase activity. Impairment of this negative modulation during ischemia may induce cardiac arrhythmias. Our study may provide a novel mechanism for ischemia-induced cardiac injury.