Faculty Profiles - WATANABE Shogo

Bile Acid Metabolism is an Intermediary Factor between Non-Alcoholic Steatohepatitis and Ischemic Heart Disease in SHRSP5/Dmcr Rats Reviewed

Shota Kumazaki, Mayu Nakamura, Shun Sasaki, Rina Tagashira, Nozomi Maruyama, Ikumi Sato, Shusei Yamamoto, Shang Ran, Shinichi Usui, Ryoko Shinohata, Takashi Ohtsuki, Satoshi Hirohata, Kazuya Kitamori, Mari Mori, Yukio Yamori, Shogo Watanabe

Journal of Nutrition & Food Sciences 09 ( 04 ) 2019.10

Non-alcoholic steatohepatitis aggravates nitric oxide synthase inhibition-induced arteriosclerosis in SHRSP5/Dmcr rat model Reviewed

Shogo Watanabe, Shota Kumazaki, Shusei Yamamoto, Ikumi Sato, Kazuya Kitamori, Mari Mori, Yukio Yamori, Satoshi Hirohata

International Journal of Experimental Pathology 2019.1

Non-alcoholic steatohepatitis aggravates nitric oxide synthase inhibition-induced arteriosclerosis in SHRSP5/Dmcr rat model. Reviewed International journal

Shogo Watanabe, Shota Kumazaki, Shusei Yamamoto, Ikumi Sato, Kazuya Kitamori, Mari Mori, Yukio Yamori, Satoshi Hirohata

International journal of experimental pathology 99 ( 6 ) 282 - 294 2018.12

Language：English Publishing type：Research paper (scientific journal)

Non-alcoholic steatohepatitis (NASH) is linked to increased cardiovascular risk, independent of the broad spectrum of metabolic syndrome risk factors. Stroke-prone (SP) spontaneously hypertensive rats (SHRSP5/Dmcr) fed a high-fat and high-cholesterol (HFC) diet developed hepatic lesions similar to those in human NASH pathology. These rats simultaneously developed lipid deposits in the mesenteric arteries, cardiac fibrosis, endothelial dysfunction and left ventricle (LV) diastolic dysfunction. However, the intermediary factors between NASH and cardiovascular disease are still unknown. We investigated whether NASH aggravates nitric oxide (NO) synthase inhibition-induced arteriosclerosis in SHRSP5/Dmcr rats. Wistar Kyoto and SHRSP5/Dmcr rats were divided into 4 groups of 5 and fed the stroke-prone (SP) or HFC diets for 8 weeks. To induce NO synthase inhibition, Nω -nitro-L-arginine methyl ester hydrochloride (L-NAME) mixed with drinking water was administered in the final 2 weeks. The NASH+L-NAME group demonstrated the following characteristics related to arteriosclerosis and myocardial ischaemia: (a) LV systolic dysfunction with asynergy, (b) replacement fibrosis caused by the shedding of cardiomyocytes and (c) arterial lipid deposition and coronary occlusion secondary to endothelial dysfunction. These characteristics were not observed in the NASH or non-NASH+L-NAME groups. The SHRSP5/Dmcr rat model demonstrates that NASH significantly aggravates cardiovascular risk.

DOI： 10.1111/iep.12301

A high-fat and high-cholesterol diet induces cardiac fibrosis, vascular endothelial, and left ventricular diastolic dysfunction in shrsp5/dmcr rats Reviewed

Shogo Watanabe, Shota Kumazaki, Katsuhiro Kusunoki, Terumi Inoue, Yui Maeda, Shinichi Usui, Ryoko Shinohata, Takashi Ohtsuki, Satoshi Hirohata, Shozo Kusachi, Kazuya Kitamori, Mari Mori, Yukio Yamori, Hisao Oka

Journal of Atherosclerosis and Thrombosis 25 ( 5 ) 439 - 453 2018

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Atherosclerosis Society

Aim: Non-alcoholic steatohepatitis (NASH) increases cardiovascular risk regardless of risk factors in metabolic syndrome. However, the intermediary factors between NASH and vascular disease are still unknown because a suitable animal model has never been established. The stroke-prone (SP) spontaneously hypertensive rat, SHRSP5/Dmcr, simultaneously develops hypertension, acute arterial lipid deposits in mesenteric arteries, and NASH when feed with a high-fat and high-cholesterol (HFC) diet. We investigated whether SHRSP5/Dmcr affected with NASH aggravates the cardiac or vascular dysfunction. Method: Wister Kyoto and SHRSP5/Dmcr rats were divided into 4 groups of 5 rats each, and fed with a SP or HFC diet. After 8 weeks of HFC or SP diet feeding, glucose and insulin resistance, echocardiography, blood biochemistry, histopathological staining, and endothelial function in aorta were evaluated. Results: We demonstrate that SHRSP5/Dmcr rats fed with a HFC diet presented with cardiac and vascular dysfunction caused by cardiac fibrosis, endothelial dysfunction, and left ventricular diastolic dysfunction, in association with NASH and hypertension. These cardiac and vascular dysfunctions were aggravated and not associated with the presence of hypertension, glucose metabolism disorder, and/or obesity. Conclusions: SHRSP5/Dmcr rats may be a suitable animal model for elucidating the organ interaction between NASH and cardiac or vascular dysfunction.

DOI： 10.5551/jat.40956

Scopus

Novel Mechanomyogram/electromyogram Hybrid Transducer Measurements Reflect Muscle Strength during Dynamic Exercise ̶ Pedaling of Recumbent Bicycle ̶ Reviewed

Shinichi Fukuhara, Shogo Watanabe, Hisao Oka

Advanced Biomedical Engineering 7 47 - 54 2018

SHRSP5/Dmcrラットにおける循環器系の基礎病態解析 Reviewed

渡辺彰吾, 熊崎章太

SHR等疾患モデル共同研究会News letter 2018

Estimating the minimum stimulation frequency necessary to evoke tetanic progression based on muscle twitch parameters Reviewed

Shogo Watanabe, Shinichi Fukuhara, Takeshi Fujinaga, Hisao Oka

PHYSIOLOGICAL MEASUREMENT 38 ( 3 ) 466 - 476 2017.3

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：IOP PUBLISHING LTD

The summation of the muscle force caused by an increase in the firing rate is named a tetanic contraction (tetanus), and the minimum stimulation frequency necessary to evoke an unfused/fused tetanus is related to the contraction time (CT) and relaxation time (RT) of the twitch. In particular, the fusion index (FI) is a very useful indicator, and it is used to evaluate the change in the muscle fiber component ratio. However, the measurement of the FI is invasive, because most patients experience pain during the electrical stimulation for tetanus. We expect that the twitch parameters CT and RT can substitute for the FI in the future. We found that the minimum stimulation frequency necessary to evoke the unfused/fused tetanus can be estimated from the twitch parameters as a first step. The results showed that (1) the minimum stimulation frequencies calculated from twitch parameters during unfused/fused tetanus were very similar to those calculated from FI parameters, and (2) they were also strongly correlated with FI parameters regardless of fiber components. The basic characteristics of tetanic progression in different fiber types could be estimated from twitch parameters.

DOI： 10.1088/1361-6579/aa5bd1

The developed MMG / EMG Hybrid Transducer reflects Muscle Strength during Dynamic Exercise - Pedaling of Recumbent Bicycle - Reviewed

Shinichi Fukuhara, Shogo Watanabe, Hisao Oka

Advanced Biomedical Engineering 7 47 - 54 2017

Development of MMG/EMG Hybrid Transducer System with simultaneous five-channel measurement Reviewed

Fukuhara Shinichi, Watanabe Shogo, Oka Hisao

Transactions of Japanese Society for Medical and Biological Engineering 55 ( 4 ) 252 - 252 2017

Language：Japanese Publisher：Japanese Society for Medical and Biological Engineering

<p>By simultaneously measuring Mechanomyoram (MMG) and Electromyogram (EMG), it is possible to accurate assessment of skeletal muscle contraction. However, MMG measurement has been rarely used for reasons such as having to fix body. Therefore, the authors developed MMG/EMG hybrid transducer system. The device was small and light (47x34x24 mm, 34 g). It was capable of MMG/EMG measurement without requiring any accessory, because sensor section, transducer and storage were integrated. Attachment to the skin was used a dedicated belt conforming to device shape. In addition, hybrid transducer was communicated with operation terminal via Bluetooth(R), and measurement control software collectively controlled five hybrid transducers and could set measurement parameters such as sampling time. MMG/EMG waveforms were monitored in real-time, and data were output in CSV format. By MMG/EMG hybrid transducer system, everyone could simply measure regardless of any field. ACKNOWLEDGEMENT: This research was partially supported by Okayama Prefecture.</p>

DOI： 10.11239/jsmbe.55Annual.252

CiNii Article

Electrically induced mechanomyograms reflect inspiratory muscle strength in young or elderly subjects Reviewed

Shogo Watanabe, Ippei Nojima, Yuuna Agarie, Tatsunori Watanabe, Shinichi Fukuhara, Takeshi Fujinaga, Hisao Oka

Respiratory Investigation 54 ( 6 ) 436 - 444 2016.11

Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier B.V.

Background Respiratory muscle strength has been used as a tool for evaluating respiratory rehabilitation in chronic obstructive pulmonary disease. However, mouth pressure measurement evaluated by maximum expiratory mouth pressure (PEmax) or inspiratory mouth pressure (PImax) offers an indirect method for measuring respiratory muscle strength. We demonstrated the evaluation of diaphragm contractility using a mechanomyogram (MMG), which is the mechanical signal generated by the motion of the diaphragm induced by the electric stimulation of the phrenic nerve. Methods Study participants were 21 young and 20 elderly subjects with no symptoms of respiratory disease. The elderly subjects were divided into non-smoker or smoker groups. The smoker group was defined as subjects having a Brinkman Index of greater than 300. We measured basic spirometric parameters, mouth pressure (PEmax, PImax), and diaphragmatic MMG. Results Diaphragmatic MMG showed more clear contrast between young subjects and elderly non-smoker or smoker subjects than the conventional method for respiratory muscle contraction (PEmax, PImax). In addition, the diaphragmatic MMG strongly correlated with inspiratory muscle strength. Conclusions Diaphragmatic MMG may reflect diaphragmatic contractility more directly and sensitively than the conventional method.

DOI： 10.1016/j.resinv.2016.06.001

Scopus

Enhancement of arterial pulsation during flow-mediated dilation is impaired in the presence of ischemic heart disease Reviewed

Eisuke Amiya, Masafumi Watanabe, Shogo Watanabe, Munenori Takata, Issei Komuro

SPRINGERPLUS 5 ( 1 ) 2016.7

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER INTERNATIONAL PUBLISHING AG

Purpose: The aim of this study is to investigate the relationship between arterial pulse amplitude change under increased shear stress and the presence of ischemic heart disease (IHD).
Methods: This study comprised 31 subjects, including 14 subjects with IHD. We investigated the change in brachial artery pulse amplitude during flow-mediated dilation (FMD) using ultrasonography.
Results: The arterial pulse amplitude increased during FMD in 19 subjects, whereas it decreased in 12 subjects. There was a marked difference in the change in arterial pulse amplitude (the maximum amplitude of the arterial pulse amplitude during FMD/the arterial pulse amplitude at baseline) between subjects with and without IHD (0.98 +/- 0.53 and 1.37 +/- 0.53, p = 0.028). Furthermore, decreased arterial pulse amplitude during FMD was a significant predictor of IHD after adjustment of age, blood pressure, the presence of each type of coronary risks, the value of FMD and sex (p = 0.0001).
Conclusions: The decrease of arterial pulsation amplitude during FMD was a useful predictive parameter for IHD.

DOI： 10.1186/s40064-016-2794-0

Enhancement of arterial pulsation during flow-mediated dilation is impaired in the presence of ischemic heart disease Reviewed

Eisuke Amiya, Masafumi Watanabe, Shogo Watanabe, Munenori Takata, Issei Komuro

SPRINGERPLUS 5 ( 1103 ) 2016.7

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER INTERNATIONAL PUBLISHING AG

DOI： 10.1186/s40064-016-2794-0

横隔膜筋音図と呼吸筋力の関係 Reviewed

渡辺彰吾, 福原真一, 藤長武士, 岡久雄

電子情報通信学会技術研究報告 116 ( 170 ) 25 - 28 2016.7

Evaluation of Skeletal Muscle Contraction during Pedaling of Recumbent Bicycle using MMG / EMG Hybrid Transducer Reviewed

FUKUHARA Shinichi, FUJINAGA Takeshi, WATANABE Shogo, OKA Hisao

Transactions of Japanese Society for Medical and Biological Engineering 54 ( PROC ) 1 - 2 2016

Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Society for Medical and Biological Engineering

<p>Electromyogram (EMG) is recorded electrical muscle contraction, mechanomyogram (MMG) indicates cross-sectional area change of muscle, reflect mechanical muscle contraction. By simultaneously measuring both signals, it is possible to multifaceted evaluation of muscle contraction. However, MMG measurement at voluntary movement was difficult. Therefore, the authors developed MMG / EMG hybrid transducer capable of simultaneous measurement of MMG and EMG. This study evaluated MMG and EMG of rectus femoris (RF) and hamstrings using recumbent bicycle of easy load regulation. As result, dMMGbase (baseline of displacement MMG) indicated cross-sectional area change of muscle at pushing down and pulling up of pedal. In addition, EMG and dMMGbase increased with pushing down of pedal in RF, dMMGacc (acceleration dMMGbase) showing muscle contraction force was output simultaneously. Each signal of hamstrings had output that antagonize RF. By simultaneously measuring MMG and EMG at recumbent bicycle pedaling, it was possible to evaluate muscle contraction of voluntary movement.</p>

DOI： 10.11239/jsmbe.54Annual.P2-C04-1

CiNii Article

Blockade of glucocorticoid receptors with RU486 attenuates cardiac damage and adipose tissue inflammation in a rat model of metabolic syndrome Reviewed

Yuuri Takeshita, Shogo Watanabe, Takuya Hattori, Kai Nagasawa, Natsumi Matsuura, Keiji Takahashi, Toyoaki Murohara, Kohzo Nagata

HYPERTENSION RESEARCH 38 ( 11 ) 741 - 750 2015.11

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

Glucocorticoids are stress hormones that modulate metabolic, inflammatory and cardiovascular processes. We recently characterized DahlS. Z-Leprfa/Leprfa (DS/obese) rats, derived from a cross between Dahl salt-sensitive (DS) and Zucker rats, as a new animal model of metabolic syndrome (MetS). We have now investigated the effects of glucocorticoid receptor (GR) blockade on cardiac and adipose tissue pathology and gene expression, as well as on glucose metabolism in this model. DS/obese rats were treated with the GR blocker RU486 (2 mg kg(-1) per day, subcutaneous) for 4 weeks beginning at 9 weeks of age. Age-matched homozygous lean (DahlS. Z-Lepr(+)/Lepr(+), or DS/lean) littermates of DS/obese rats served as controls. Treatment of DS/obese rats with RU486 attenuated left ventricular (LV) fibrosis and diastolic dysfunction, as well as cardiac oxidative stress and inflammation, without affecting hypertension or LV hypertrophy. Administration of RU486 to DS/obese rats also inhibited the upregulation of GR and 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) expression at the mRNA and protein levels in the heart; it attenuated adiposity and adipose tissue inflammation, as well as the upregulation of GR and 11 beta-HSD1 mRNA and protein expression in adipose tissue; it ameliorated fasting hyperinsulinemia as well as insulin resistance and glucose intolerance. Our results thus implicate the glucocorticoid-GR axis in the pathophysiology of MetS, and they suggest that GR blockade has therapeutic potential for the treatment of this condition.

DOI： 10.1038/hr.2015.77

Restraint stress exacerbates cardiac and adipose tissue pathology via beta-adrenergic signaling in rats with metabolic syndrome Reviewed

Natsumi Matsuura, Kai Nagasawa, Yuji Minagawa, Shogo Ito, Yusuke Sano, Yuichiro Yamada, Takuya Hattori, Shogo Watanabe, Toyoaki Murohara, Kohzo Nagata

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY 308 ( 10 ) H1275 - H1286 2015.5

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER PHYSIOLOGICAL SOC

Restraint stress stimulates sympathetic nerve activity and can affect adiposity and metabolism. However, the effects of restraint stress on cardiovascular and metabolic disorders in metabolic syndrome (MetS) have remained unclear. We investigated the effects of chronic restraint stress and beta-adrenergic receptor (beta-AR) blockade on cardiac and adipose tissue pathology and metabolic disorders in a rat model of MetS. DahlS. Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats. Rats were exposed to restraint stress (restraint cage, 2 h/day) for 4 wk from 9 wk of age with or without daily subcutaneous administration of the beta-AR blocker propranolol (2 mg/kg). Age-matched homozygous lean littermates of DS/obese rats (DahlS. Z-Lepr(+)/Lepr(+) rats) served as control animals. Chronic restraint stress exacerbated hypertension as well as left ventricular hypertrophy, fibrosis, diastolic dysfunction, and oxidative stress in a manner sensitive to propranolol treatment. Restraint stress attenuated body weight gain in DS/obese rats, and this effect tended to be reversed by propranolol (P = 0.0682). Restraint stress or propranolol did not affect visceral or subcutaneous fat mass. However, restraint stress potentiated cardiac and visceral adipose tissue inflammation in DS/obese rats, and these effects were ameliorated by propranolol. Restraint stress also exacerbated glucose intolerance, insulin resistance, and abnormal lipid metabolism in a manner sensitive to propranolol. In addition, restraint stress increased urinary norepinephrine excretion, and propranolol attenuated this effect. Our results thus implicate beta-ARs in the exacerbation of cardiac and adipose tissue pathology and abnormal glucose and lipid metabolism induced by restraint stress in this model of MetS.

DOI： 10.1152/ajpheart.00906.2014

ROLES OF OXIDATIVE STRESS AND THE MINERALOCORTICOID RECEPTOR IN CARDIAC PATHOLOGY IN A RAT MODEL OF METABOLIC SYNDROME Reviewed

Keiji Takahashi, Tamayo Murase, Miwa Takatsu, Natsumi Matsuura, Kai Nagasawa, Takuya Hattori, Shogo Watanabe, Toyoaki Murohara, Kohzo Nagata

NAGOYA JOURNAL OF MEDICAL SCIENCE 77 ( 1-2 ) 275 - 289 2015.2

Language：English Publishing type：Research paper (scientific journal) Publisher：NAGOYA UNIV, SCH MED

Oxidative stress and the mineralocorticoid receptor (MR) are implicated in the pathogenesis of salt-induced left ventricular (LV) diastolic dysfunction associated with metabolic syndrome (MetS). We recently characterized DahlS. Z-Leprfa/Leprfa (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats, as a new animal model of MetS. We investigated the pathophysiological roles of increased oxidative stress and MR activation in cardiac injury with this model. DS/obese rats were treated with the antioxidant tempol (1 mmol/L in drinking water) or the selective MR antagonist eplerenone (15 mg/kg per day, per os) for 5 weeks beginning at 10 weeks of age. The increased systolic blood pressure and LV hypertrophy that develop in untreated DS/obese rats were substantially ameliorated by eplerenone but not by tempol. Eplerenone also attenuated LV fibrosis and diastolic dysfunction more effectively than did tempol in DS/obese rats, whereas cardiac oxidative stress and inflammation were reduced similarly by both drugs. Both the ratio of plasma aldosterone concentration to plasma renin activity and cardiac expression of the MR and serum/glucocorticoid-regulated kinase 1 genes were decreased to a greater extent by eplerenone than by tempol. Our results indicate that both increased oxidative stress and MR activation in the heart may contribute to the development of LV remodeling and diastolic dysfunction in DS/obese rats. The superior cardioprotective action of eplerenone is likely attributable to its greater antihypertensive effect, which is likely related to its greater inhibition of aldosterone-MR activity in the cardiovascular system.

Comparative effects of valsartan in combination with cilnidipine or amlodipine on cardiac remodeling and diastolic dysfunction in Dahl salt-sensitive rats Reviewed

Kai Nagasawa, Keiji Takahashi, Natsumi Matsuura, Miwa Takatsu, Takuya Hattori, Shogo Watanabe, Eri Harada, Kazumi Niinuma, Toyoaki Murohara, Kohzo Nagata

HYPERTENSION RESEARCH 38 ( 1 ) 39 - 47 2015.1

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

Angiotensin receptor blockers (ARBs) are often supplemented with calcium channel blockers (CCBs) for treatment of hypertension. We recently showed that the L/N-type CCB cilnidipine has superior cardioprotective effects compared with the L-type CCB amlodipine in Dahl salt-sensitive (DS) rats. We have now compared the effects of the ARB valsartan combined with cilnidipine or amlodipine on cardiac pathophysiology in DS rats. DS rats fed a high-salt diet from 6 weeks of age were treated with vehicle, valsartan alone (10 mg kg(-1) per day), or valsartan combined with either cilnidipine (1 mg kg(-1) per day) or amlodipine (1 mg kg(-1) per day) from 7 to 11 weeks. The salt-induced increase in systolic blood pressure apparent in the vehicle group was attenuated similarly in the three drug treatment groups. Valsartan-cilnidipine attenuated left ventricular (LV) fibrosis and diastolic dysfunction as well as cardiac oxidative stress and inflammation to a greater extent than did valsartan alone or valsartan-amlodipine. In addition, the increases in urinary excretion of dopamine and epinephrine as well as in cardiac renin-angiotensin-aldosterone-system (RAAS) gene expression apparent in vehicle-treated rats were attenuated to a greater extent by valsartan-cilnidipine than by the other two treatments. Valsartan-cilnidipine thus attenuated LV remodeling and diastolic dysfunction more effectively than did valsartan or valsartan-amlodipine in rats with salt-sensitive hypertension, and this superior cardioprotective action of valsartan-cilnidipine compared with valsartan-amlodipine is likely attributable, at least in part, to the greater antioxidant and antiinflammatory effects associated with both greater inhibition of cardiac RAAS gene expression and N-type calcium channel blockade.

DOI： 10.1038/hr.2014.136