| 1. |
Ikeda S, Shinohara K, Kashihara S, Matsumoto S, Yoshida D, Nakashima R, Ono Y, Nishihara M, Katsurada K, Tsutsui H, Contribution of afferent renal nerve signals to acute and chronic blood pressure regulation in stroke-prone spontaneously hypertensive rats, Hypertension Research, 2023.01. |
| 2. |
Tomohiko Akahoshi, Noriyuki Kaku, Yuji Shono, Yuzo Yamamoto, Keita Takahashi, Takeshi Iyonaga, Kenta Momii, Masaaki Nishihara, Jun Maki, Kentaro Tokuda, Ken Yamaura, Impact of Antithrombin Activity Levels Following Recombinant Antithrombin Gamma Therapy in Patients with Sepsis-Induced Disseminated Intravascular Coagulation, Clinical and Applied Thrombosis/Hemostasis, 2022.11. |
| 3. |
Yuji Shono, Satomi Mezuki, Tomohiko Akahoshi, Masaaki Nishihara, Noriyuki Kaku, Jun Maki, Kentaro Tokuda, Takanari Kitazono, Prediction of intracranial lesions in patients with consciousness disturbance by ultrasonography in the intensive care unit, The Journal of International Medical Research, 2022.09. |
| 4. |
Masaaki Nishihara, Ken-Ichi Hiasa, Nobuyuki Enzan, Kenzo Ichimura, Takeshi Iyonaga, Yuji Shono, Masahiro Kashiura, Takashi Moriya, Takanari Kitazono, Hiroyuki Tsutsui, Hyperoxemia is Associated With Poor Neurological Outcomes in Patients With Out-of-Hospital Cardiac Arrest Rescued by Extracorporeal Cardiopulmonary Resuscitation: Insight From the Nationwide Multicenter Observational JAAM-OHCA (Japan Association for Acute Medicine) Registry., The Journal of Emergency Medicine, 2022.08. |
| 5. |
Nobuyuki Enzan, Ken Ichi Hiasa, Kenzo Ichimura, Masaaki Nishihara, Takeshi Iyonaga, Yuji Shono, Takeshi Tohyama, Kouta Funakoshi, Takanari Kitazono, Hiroyuki Tsutsui, Delayed administration of epinephrine is associated with worse neurological outcomes in patients with out-of-hospital cardiac arrest and initial pulseless electrical activity: insight from the nationwide multicentre observational JAAM-OHCA (Japan Association for Acute Medicine) registry, European Heart Journal - Acute Cardiovascular Care, 2022.06. |
| 6. |
Masahiro Kashiura, Hideto Yasuda, Yuki Kishihara, Keiichiro Tominaga, Masaaki Nishihara, Ken‑ichi Hiasa, Hiroyuki Tsutsui, Takashi Moriya, Association between short-term neurological outcomes and extreme hyperoxia in patients with out-of-hospital cardiac arrest who underwent extracorporeal cardiopulmonary resuscitation: a retrospective observational study from a multicenter registry, BMC Cardiovascular Disorders, 2022.04. |
| 7. |
Yoshinobu Murasato, Masaaki Nishihara, Takahiro Mori, Kyohei Meno, Kodai Shibao, Katsuhiko Takenaka, Kiyotaka Iwasaki, Feasibility and efficacy of an ultra-short side branch-dedicated balloon in coronary bifurcation stenting, EuroIntervention, 2021;17(5):e425-e432., 2021.08. |
| 8. |
Ryosuke Nakashima, Masaaki Nishihara, Takeshi Iyonaga, Sho Iwasaka Yuzo Yamamoto, Yuji Shono, Jun Maki, Kentaro Tokuda, Tomohiko Akahoshi, Taiki Higo, Takanari Kitazono, Hiroyuki Tsutsui, Efficacy of thromboelastography in the management of anticoagulation for veno-venous extracorporeal membrane oxygenation in a coronavirus disease 2019 patient: A case report, Medicine, 2021;100(23):e26313., 2021.06. |
| 9. |
Masaaki Nishihara, Ko Takesue, Yoshitaka Hirooka, Olmesartan combined with renal denervation reduces blood pressure in association with sympatho-inhibitory and aldosterone-reducing effects in hypertensive mice with chronic kidney disease, Clinical and Experimental Hypertension, 10.1080/10641963.2018.1465075, 41, 3, 211-219, 2019.04, Background: Augmented sympathetic nerve activity (SNA) and renin-angiotensin-aldosterone system (RAAS) activity are involved in the pathogenesis of hypertension (HT) accompanied by chronic kidney disease (CKD). Oxidative stress in the hypothalamus increases SNA in HT. Administration of an angiotensin ΙΙ receptor blocker (olmesartan; OLM) or renal denervation (RDN) exerts an antihypertensive effect in HT with CKD; however, the precise mechanisms of the combination therapy are not fully elucidated. In the present study, we examined whether combination therapy with OLM and RDN reduces both SNA by decreasing oxidative stress in the hypothalamus and RAAS activity in hypertensive mice with CKD. Methods and Results: In 5/6-nephrectomized ICR-mice (Nx-mice) at 4-weeks after nephrectomy, systolic blood pressure (SBP) was significantly increased, accompanied by increased SNA and albuminuria compared with control-mice. Nx-mice were orally administered OLM, vehicle, or underwent RDN during OLM administration, and divided into Nx-OLM, Nx-VEH, and Nx-OLM/RDN groups, respectively. In Nx-OLM and Nx-OLM/RDN compared with Nx-VEH at 8-weeks after treatment, SBP was significantly decreased and both SNA and oxidative stress levels in the hypothalamus were significantly suppressed, without worsened creatinine clearance. In Nx-OLM and Nx-OLM/RDN compared with Nx-VEH, albuminuria was also suppressed, and the heart per body weight was decreased. In Nx-OLM/RDN, but not in Nx-OLM, the plasma aldosterone concentration was significantly decreased compared with Nx-VEH. Conclusion: These findings suggest that combination therapy with OLM/RDN has antihypertensive effects in association with suppressing SNA by reducing oxidative stress in the hypothalamus and the plasma aldosterone concentration in hypertensive mice with CKD.. |
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Masaaki Nishihara, Ko Takesue, Yoshitaka Hirooka, Renal denervation enhances GABA-ergic input into the PVN leading to blood pressure lowering in chronic kidney disease, Autonomic Neuroscience: Basic and Clinical, 10.1016/j.autneu.2016.09.018, 204, 88-97, 2017.05, Objective Sympathoexcitation plays an important role in the pathogenesis of hypertension in patients with chronic kidney disease (CKD). The paraventricular nucleus of the hypothalamus (PVN) in the brain controls sympathetic outflow through γ-amino butyric acid (GABA)-ergic mechanisms. Renal denervation (RDN) exerts a long-term antihypertensive effect in hypertension with CKD; however, the effects of RDN on sympathetic nerve activity and GABA-ergic modulation in the PVN are not clear. We aimed to elucidate whether RDN modulates sympathetic outflow through GABA-ergic mechanisms in the PVN in hypertensive mice with CKD. Methods and results In 5/6-nephrectomized male Institute of Cancer Research mice (Nx) at 4 weeks after nephrectomy, systolic blood pressure (SBP) was significantly increased, accompanied by sympathoexcitation. The Nx-mice underwent RDN or sham operation, and the mice were divided into three groups (Control, Nx-Sham, and Nx-RDN). At 2 weeks after RDN, SBP was significantly decreased and urinary sodium excretion was increased in Nx-RDN compared with Nx-Sham. Urinary norepinephrine excretion (uNE) levels did not differ significantly between Nx-RDN and Nx-Sham. At 6 weeks after RDN, SBP continued to decrease and uNE levels also decreased in Nx-RDN compared with Nx-Sham. Bicuculline microinjection into the PVN increased mean arterial pressure and lumbar sympathetic nerve activity in all groups. The pressor responses and change in lumbar sympathetic nerve activity were significantly attenuated in Nx-Sham, but were enhanced in Nx-RDN at 6 weeks after RDN. Conclusions The findings from the present study indicate that RDN has a prolonged antihypertensive effect and, at least in the late phase, decreases sympathetic nerve activity in association with enhanced GABA-ergic input into the PVN in mice with CKD.. |
| 11. |
Masaaki Nishihara, Yoshitaka Hirooka, The mechanism of blood pressure regulation by the central nervous system, Nippon rinsho. Japanese journal of clinical medicine, 73, 11, 1798-1800, 2015.11. |
| 12. |
Masaaki Nishihara, Yoshitaka Hirooka, Kenji Sunagawa, Combining irbesartan and trichlormethiazide enhances blood pressure reduction via inhibition of sympathetic activity without adverse effects on metabolism in hypertensive rats with metabolic syndrome, Clinical and Experimental Hypertension, 10.3109/10641963.2014.897719, 37, 1, 33-38, 2015.02, Sympathoexcitation and oxidative stress in the brain have pivotal roles in hypertension with metabolic syndrome (MetS). Here, we examined whether oral administration of irbesartan (IRB) and trichlormethiazide (TCM) decreases blood pressure (BP) via inhibiting sympathetic activity through anti-oxidant effects in the brain of spontaneously hypertensive rats (SHR-cp). IRB/TCM treatment decreased BP more profoundly than IRB monotherapy. Urinary norepinephrine excretion and oxidative stress in the brain were decreased in both IRB and IRB/TCM groups without any adverse effect on the metabolic profile. These findings suggest that IRB/TCM profoundly decreases BP in SHR-cp by inhibiting sympathetic activity via anti-oxidant effects in the brain.. |
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Masaaki Nishihara, Yoshitaka Hirooka, [Effect of sympathetic nervous system on circadian rhythm of blood pressure]., Nippon rinsho. Japanese journal of clinical medicine, 72, 8, 1374-1378, 2014, There is evidence that the abnormal circadian rhythm of blood pressure (BP), such as absent of nocturnal BP fall and exaggerated morning BP surge, assessed by ambulatory BP monitoring is associated with cardiovascular events independent of BP levels in hypertensive patients. The activation of the sympathetic nervous system (SNS) is one of the most important pathophysiological mechanisms underlying abnormalities in circadian BP by affecting cardiac output, salt and volume balance in the kidney, and peripheral vascular resistance. In treating hypertension, especially accompanied by the abnormal circadian rhythm of BP, the effect of antihypertensive drug on SNS activity, as well as the timing of drug administration or the duration of the drug efficacy, should be considered.. |
| 14. |
Masaaki Nishihara, Yoshitaka Hirooka, Takuya Kishi, Kenji Sunagawa, Different role of oxidative stress in paraventricular nucleus and rostral ventrolateral medulla in cardiovascular regulation in awake spontaneously hypertensive rats, Journal of hypertension, 10.1097/HJH.0b013e32835613d7, 30, 9, 1758-1765, 2012.09, Objective: The rostral ventrolateral medulla (RVLM) of the brainstem and the paraventricular nucleus of the hypothalamus (PVN) are involved in the neural mechanisms of hypertension. Oxidative stress in the RVLM contributes to the enhanced central sympathetic outflow that leads to hypertension in experimental models of hypertension, such as spontaneously hypertensive rats (SHRs). We investigated the relative contribution of oxidative stress in the PVN and RVLM of SHR in blood pressure (BP) regulation. METHODS AND Results: We transfected adenovirus vectors encoding the manganese superoxide dismutase gene (AdMnSOD) or β-galactosidase gene (AdLacZ) bilaterally into the RVLM or PVN. Mean arterial pressure (MAP) and heart rate (HR) were monitored using a radiotelemetry system. Oxidative stress levels in the PVN of SHR evaluated by thiobarbituric acid-reactive substances were enhanced compared with those of Wistar-Kyoto rats and reduced by MnSOD transfection compared with nontransfected SHR. MAP and HR of AdMnSOD-RVLM-transfected SHR were decreased compared with AdLacZ-RVLM-transfected SHR. In contrast, MAP of AdMnSOD-PVN-transfected SHR was not decreased compared with AdLacZ-PVN-transfected SHR, but HR was decreased compared with AdLacZ-PVN-transfected SHR. MnSOD transfection into both the RVLM and PVN of SHR decreased MAP and elicited a profound decrease in HR. Conclusion: These findings indicate that inhibition of oxidative stress in the PVN decreases HR, but not BP in SHR, and elicits a further decrease in HR, but not BP, by interacting with the RVLM. Taken together, the oxidative stress in the PVN and RVLM plays a different role for cardiovascular regulation in SHR.. |
| 15. |
Masaaki Nishihara, Yoshitaka Hirooka, Ryuichi Matsukawa, Takuya Kishi, Kenji Sunagawa, Oxidative stress in the rostral ventrolateral medulla modulates excitatory and inhibitory inputs in spontaneously hypertensive rats, Journal of hypertension, 10.1097/HJH.0b013e32834e1df4, 30, 1, 97-106, 2012.01, Objectives: The rostral ventrolateral medulla (RVLM) of the brainstem and the paraventricular nucleus (PVN) of the hypothalamus play crucial roles in central cardiovascular regulation. In hypertensive rats, an imbalance of excitatory and inhibitory inputs to the RVLM enhances central sympathetic outflow. Increased reactive oxygen species (ROS) in the RVLM also contribute to sympathoexcitation, leading to hypertension. The aim of the present study was to elucidate whether ROS in the RVLM modulate synaptic transmission via excitatory and inhibitory amino acids and influence the excitatory inputs to the RVLM from the PVN in spontaneously hypertensive rats (SHRs). METHODS AND Results: We transfected adenovirus vectors encoding the manganese superoxide dismutase (AdMnSOD) gene to scavenge ROS in the RVLM both in Wistar-Kyoto rats and SHRs. The decreases in blood pressure and renal sympathetic nerve activity (RSNA) evoked by injecting kynurenic acid, a glutamate receptor blocker, into the RVLM were attenuated, and the increases in blood pressure and RSNA evoked by injecting bicuculline, a γ-amino butyric acid (GABA) receptor blocker, into the RVLM were enhanced in AdMnSOD-transfected SHRs compared with adenovirus vectors encoding the β-galactosidase (AdLacZ) gene-transfected SHRs. Furthermore, the increases in blood pressure and RSNA evoked by injecting bicuculline into the PVN were attenuated in AdMnSOD-transfected SHRs compared with AdLacZ-transfected SHRs. Conclusion: These findings suggest that ROS in the RVLM enhance glutamatergic excitatory inputs and attenuate GABAergic inhibitory inputs to the RVLM, thereby increasing sympathoexcitatory input to the RVLM from the PVN in SHRs.. |
