Murakami Manabu, Yoshikawa Takeo, Nakamura Tadaho, Ohba Takayoshi, Matsuzaki Yasushi, Sawamura Daisuke, Kuwasako Kenji, Yanagisawa Teruyuki, Ono Kyouichi, Nakaji Shigeyuki, Yanai Kazuhiko
Department of Pharmacology, Hirosaki University, Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan.
Department of Pharmacology, Tohoku University School of Medicine, Seiryo-machi 2-1, Aoba-Ku, Sendai, 980-8575, Japan.
Biochem Biophys Res Commun. 2015 Mar 13;458(3):584-589. doi: 10.1016/j.bbrc.2015.02.009. Epub 2015 Feb 11.
The histamine system is involved in the regulation of the autonomic nervous system. We used gene-targeted mice to investigate the role of histamine receptors in the regulation of the sympathetic nervous system. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed histamine H1, H2, and H3 receptor expression in the superior cervical ganglion, which contains sympathetic nerve cell bodies. We measured the heart rate variability (HRV), the changes in the beat-to-beat heart rate, which is widely used to assess autonomic activity in the heart. H1 blockade attenuated the baroreflex-mediated changes in heart rate in wild-type (WT) mice, whereas the heart rate response to H2- and H3-specific blockers was unaffected. l-Histidine decarboxylase (HDC) expression in the superior cervical ganglion of H1R-null mice was higher than that in WT controls, whereas the enzyme levels in H2R- and H3R-null mice were not significantly different from those in the WT. All mutant mice (H1R-, H2R-, and H3R-null mice) showed normal electrocardiogram (ECG) patterns with little modification in ECG parameters and the expected response to the β-adrenergic blocker propranolol. Similar to our findings in WT mice, H1 blockade attenuated the baroreflex-mediated heart rate change in H1R-null mice, whereas the heart rate response was unaffected in H2R- and H3R-null mice. The HRV analysis revealed relatively unstable RR intervals, an increased standard deviation of the interbeat interval (SDNN), and low-frequency (LF) component in H1R-null mice compared with the other groups, suggesting that sympathetic nerve activity was altered in H1R-null mice. Taken together, our findings indicate that H1 receptors play a major role in the regulation of sympathetic nerve activity.
组胺系统参与自主神经系统的调节。我们使用基因靶向小鼠来研究组胺受体在交感神经系统调节中的作用。逆转录-聚合酶链反应（RT-PCR）分析显示，在含有交感神经细胞体的颈上神经节中存在组胺H1、H2和H3受体表达。我们测量了心率变异性（HRV），即逐搏心率的变化，它被广泛用于评估心脏的自主活动。H1受体阻断减弱了野生型（WT）小鼠压力反射介导的心率变化，而对H2和H3特异性阻断剂的心率反应未受影响。H1R基因敲除小鼠颈上神经节中的L-组氨酸脱羧酶（HDC）表达高于WT对照组，而H2R和H3R基因敲除小鼠中的酶水平与WT组无显著差异。所有突变小鼠（H1R、H2R和H3R基因敲除小鼠）的心电图（ECG）模式均正常，ECG参数变化不大，对β-肾上腺素能阻滞剂普萘洛尔的反应符合预期。与我们在WT小鼠中的发现相似，H1受体阻断减弱了H1R基因敲除小鼠压力反射介导的心率变化，而H2R和H3R基因敲除小鼠的心率反应未受影响。HRV分析显示，与其他组相比，H1R基因敲除小鼠的RR间期相对不稳定，心跳间期标准差（SDNN）增加，低频（LF）成分增加，这表明H1R基因敲除小鼠的交感神经活动发生了改变。综上所述，我们的研究结果表明H1受体在交感神经活动的调节中起主要作用。
