title: Involvement of the histamine H1 receptor in the regulation of sympathetic nerve activity.
abstract: 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.
authors: Department of Pharmacology, Hirosaki University, Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan. Electronic address: mmura0123@hotmail.co.jp.
authors: Manabu
authors: M
authors: Murakami
authors: Department of Pharmacology, Tohoku University School of Medicine, Seiryo-machi 2-1, Aoba-Ku, Sendai, 980-8575, Japan.
authors: Takeo
authors: T
authors: Yoshikawa
authors: Department of Pharmacology, Tohoku University School of Medicine, Seiryo-machi 2-1, Aoba-Ku, Sendai, 980-8575, Japan.
authors: Tadaho
authors: T
authors: Nakamura
authors: Department of Cellphysiology, Akita University School of Medicine, Akita, 010-8543, Japan.
authors: Takayoshi
authors: T
authors: Ohba
authors: Department of Dermatology, Hirosaki University, Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan.
authors: Yasushi
authors: Y
authors: Matsuzaki
authors: Department of Dermatology, Hirosaki University, Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan.
authors: Daisuke
authors: D
authors: Sawamura
authors: Division for Identification and Analysis of Bioactive Peptides, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
authors: Kenji
authors: K
authors: Kuwasako
authors: Department of Molecular Pharmacology, Tohoku University School of Medicine, Seiryo-machi 2-1, Aoba-Ku, Sendai, 980-8575, Japan.
authors: Teruyuki
authors: T
authors: Yanagisawa
authors: Department of Cellphysiology, Akita University School of Medicine, Akita, 010-8543, Japan.
authors: Kyouichi
authors: K
authors: Ono
authors: Social Medicine, Hirosaki University, Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan.
authors: Shigeyuki
authors: S
authors: Nakaji
authors: Department of Pharmacology, Tohoku University School of Medicine, Seiryo-machi 2-1, Aoba-Ku, Sendai, 980-8575, Japan.
authors: Kazuhiko
authors: K
authors: Yanai
mesh_terms: D000818:Animals; D004562:Electrocardiography; D017353:Gene Deletion; D006339:Heart Rate; D006632:Histamine / Q000378:metabolism; D006640:Histidine Decarboxylase / Q000235:genetics; D051379:Mice; D011968:Receptors, Histamine / Q000235:genetics / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000235:genetics / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D006632:Histamine; D006640:Histidine Decarboxylase
keywords: Autonomic nerves; ECG; Histamine; Mouse; Sympathetic nerves