TY - JOUR
T1 - Involvement of the histamine H1 receptor in the regulation of sympathetic nerve activity
AU - Murakami, Manabu
AU - Yoshikawa, Takeo
AU - Nakamura, Tadaho
AU - Ohba, Takayoshi
AU - Matsuzaki, Yasushi
AU - Sawamura, Daisuke
AU - Kuwasako, Kenji
AU - Yanagisawa, Teruyuki
AU - Ono, Kyouichi
AU - Nakaji, Shigeyuki
AU - Yanai, Kazuhiko
N1 - Funding Information:
Our research was sponsored in part by Grants-in-Aid for Scientific Research from JSPS , KAKENHI ( 25460293 ), The Center of Healthy Aging Innovation (COI), the Special Project of Three Northern Tohoku Universities , and a program titled “Influence of socio-environmental factors on the progression of atherosclerosis among the general population”.
Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.
PY - 2015/3/13
Y1 - 2015/3/13
N2 - 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.
AB - 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.
KW - Autonomic nerves
KW - ECG
KW - Histamine
KW - Mouse
KW - Sympathetic nerves
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U2 - 10.1016/j.bbrc.2015.02.009
DO - 10.1016/j.bbrc.2015.02.009
M3 - Article
C2 - 25680462
AN - SCOPUS:84924043455
VL - 458
SP - 584
EP - 589
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -