Pharmacological Stimulation of Type 5 Adenylyl Cyclase Stabilizes Heart Rate Under Both Microgravity and Hypergravity Induced by Parabolic Flight
Pharmacological Stimulation of Type 5 Adenylyl Cyclase Stabilizes Heart Rate Under Both Microgravity and Hypergravity Induced by Parabolic Flight
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DOI：
10.1254/jphs.12102fp
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发表时间：
2012-08-01
影响因子：
3.5
通讯作者：
Okumura, Satoshi
中科院分区：
文献类型：
--
作者：
Bai, Yunzhe;Tsunematsu, Takashi;Okumura, Satoshi
我们以前证明，5型腺苷酸环化酶（AC 5）的功能，在心脏的自主调节。基于这项工作，我们假设AC 5活性的药理学调节可以调节微重力和超重力下心率的自主控制。为了验证这一假设，我们选择了用选择性AC 5激活剂（NKH 477）或抑制剂（阿糖腺苷）激活小鼠AC 5活性的方法，并检查抛物线飞行期间的心率变异性。正常R-R间期的标准差（总自主神经变异性的标志物）在阿糖腺苷组的微重力和超重力下显著更大，而NKH 477组没有显著变化，表明阿糖腺苷组的自主神经调节不稳定。心率变异性分析中的低频和高频（HF）比率（交感神经活动的标志物）在NKH 477组的微重力和超重力下显著降低，而阿糖腺苷组没有这种降低。在NKH 477组中，在微重力和超重力下，正常化的HF（副交感神经活动的标志物）显著增加。相比之下，阿糖胞苷组没有这种增加。这项研究首次表明，在微重力和超重力条件下对AC 5活性的药理学调节可能有助于调节心率的自主控制。
We previously demonstrated that type 5 adenylyl cyclase (AC5) functions in autonomic regulation in the heart. Based on that work, we hypothesized that pharmacological modulation of AC5 activity could regulate the autonomic control of the heart rate under micro- and hypergravity. To test this hypothesis, we selected the approach of activating AC5 activity in mice with a selective AC5 activator (NKH477) or inhibitor (vidarabine) and examining heart rate variability during parabolic flight. The standard deviation of normal R-R intervals, a marker of total autonomic variability, was significantly greater under micro- and hypergravity in the vidarabine group, while there were no significant changes in the NKH477 group, suggesting that autonomic regulation was unstable in the vidarabine group. The ratio of low frequency and high frequency (HF) in heart rate variability analysis, a marker of sympathetic activity, became significantly decreased under micro- and hypergravity in the NKH477 group, while there was no such decrease in the vidarabine group. Normalized HF, a marker of parasympathetic activity, became significantly greater under micro- and hypergravity in the NKH477 group. In contrast, there was no such increase in the vidarabine group. This study is the first to indicate that pharmacological modulation of AC5 activity under micro- and hypergravity could be useful to regulate the autonomic control of the heart rate.