Pharmacological Stimulation of Type 5 Adenylyl Cyclase Stabilizes Heart Rate Under Both Microgravity and Hypergravity Induced by Parabolic Flight

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 hypothe...

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Main Authors: Yunzhe Bai, Takashi Tsunematsu, Qibin Jiao, Yoshiki Ohnuki, Yasumasa Mototani, Kouichi Shiozawa, Meihua Jin, Wenqian Cai, Hui-Ling Jin, Takayuki Fujita, Yasuhiro Ichikawa, Kenji Suita, Reiko Kurotani, Utako Yokoyama, Motohiko Sato, Kousaku Iwatsubo, Yoshihiro Ishikawa, Satoshi Okumura
Format: Article
Language:English
Published: Elsevier 2012-01-01
Series:Journal of Pharmacological Sciences
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861319304827
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author Yunzhe Bai
Takashi Tsunematsu
Qibin Jiao
Yoshiki Ohnuki
Yasumasa Mototani
Kouichi Shiozawa
Meihua Jin
Wenqian Cai
Hui-Ling Jin
Takayuki Fujita
Yasuhiro Ichikawa
Kenji Suita
Reiko Kurotani
Utako Yokoyama
Motohiko Sato
Kousaku Iwatsubo
Yoshihiro Ishikawa
Satoshi Okumura
author_facet Yunzhe Bai
Takashi Tsunematsu
Qibin Jiao
Yoshiki Ohnuki
Yasumasa Mototani
Kouichi Shiozawa
Meihua Jin
Wenqian Cai
Hui-Ling Jin
Takayuki Fujita
Yasuhiro Ichikawa
Kenji Suita
Reiko Kurotani
Utako Yokoyama
Motohiko Sato
Kousaku Iwatsubo
Yoshihiro Ishikawa
Satoshi Okumura
author_sort Yunzhe Bai
collection DOAJ
description 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. Keywords:: adenylyl cyclase isoform, autonomic nerve activity, parabolic flight, heart rate variability, microgravity
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spelling doaj.art-2372b6ec37584edbb4bf036e11f53bd62022-12-21T18:44:42ZengElsevierJournal of Pharmacological Sciences1347-86132012-01-011194381389Pharmacological Stimulation of Type 5 Adenylyl Cyclase Stabilizes Heart Rate Under Both Microgravity and Hypergravity Induced by Parabolic FlightYunzhe Bai0Takashi Tsunematsu1Qibin Jiao2Yoshiki Ohnuki3Yasumasa Mototani4Kouichi Shiozawa5Meihua Jin6Wenqian Cai7Hui-Ling Jin8Takayuki Fujita9Yasuhiro Ichikawa10Kenji Suita11Reiko Kurotani12Utako Yokoyama13Motohiko Sato14Kousaku Iwatsubo15Yoshihiro Ishikawa16Satoshi Okumura17Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, JapanCardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, JapanCardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, JapanDepartment of Physiology, Tsurumi University School of Dental Medicine, Yokohama 230-8501, JapanDepartment of Physiology, Tsurumi University School of Dental Medicine, Yokohama 230-8501, JapanDepartment of Physiology, Tsurumi University School of Dental Medicine, Yokohama 230-8501, JapanCardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, JapanCardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, JapanCardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, JapanCardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, JapanCardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, JapanCardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, JapanCardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; Biochemical Engineering, Faculty of Engineering, Yamagata University, Yonezawa, Yamagata 992-8501, JapanCardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, JapanCardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, JapanCardiovascular Research Institute, Department of Cell Biology & Molecular Medicine and Medicine (Cardiology), New Jersey Medical School of UMDNJ, Newark, New Jersey 07103, USACardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; Cardiovascular Research Institute, Department of Cell Biology & Molecular Medicine and Medicine (Cardiology), New Jersey Medical School of UMDNJ, Newark, New Jersey 07103, USACardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; Department of Physiology, Tsurumi University School of Dental Medicine, Yokohama 230-8501, Japan; Corresponding author. okumura-s@tsurumi-u.ac.jp on July 31, 2012 (in advance)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. Keywords:: adenylyl cyclase isoform, autonomic nerve activity, parabolic flight, heart rate variability, microgravityhttp://www.sciencedirect.com/science/article/pii/S1347861319304827
spellingShingle Yunzhe Bai
Takashi Tsunematsu
Qibin Jiao
Yoshiki Ohnuki
Yasumasa Mototani
Kouichi Shiozawa
Meihua Jin
Wenqian Cai
Hui-Ling Jin
Takayuki Fujita
Yasuhiro Ichikawa
Kenji Suita
Reiko Kurotani
Utako Yokoyama
Motohiko Sato
Kousaku Iwatsubo
Yoshihiro Ishikawa
Satoshi Okumura
Pharmacological Stimulation of Type 5 Adenylyl Cyclase Stabilizes Heart Rate Under Both Microgravity and Hypergravity Induced by Parabolic Flight
Journal of Pharmacological Sciences
title Pharmacological Stimulation of Type 5 Adenylyl Cyclase Stabilizes Heart Rate Under Both Microgravity and Hypergravity Induced by Parabolic Flight
title_full Pharmacological Stimulation of Type 5 Adenylyl Cyclase Stabilizes Heart Rate Under Both Microgravity and Hypergravity Induced by Parabolic Flight
title_fullStr Pharmacological Stimulation of Type 5 Adenylyl Cyclase Stabilizes Heart Rate Under Both Microgravity and Hypergravity Induced by Parabolic Flight
title_full_unstemmed Pharmacological Stimulation of Type 5 Adenylyl Cyclase Stabilizes Heart Rate Under Both Microgravity and Hypergravity Induced by Parabolic Flight
title_short Pharmacological Stimulation of Type 5 Adenylyl Cyclase Stabilizes Heart Rate Under Both Microgravity and Hypergravity Induced by Parabolic Flight
title_sort pharmacological stimulation of type 5 adenylyl cyclase stabilizes heart rate under both microgravity and hypergravity induced by parabolic flight
url http://www.sciencedirect.com/science/article/pii/S1347861319304827
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