Carotid Body Denervation Markedly Improves Survival in Rats With Hypertensive Heart Failure

Fujii, Kenta; Saku, Keita; Kishi, Takuya; Oga, Yasuhiro; Tohyama, Takeshi; Nishikawa, Takuya; Sakamoto, Takafumi; Ikeda, Masataka; Ide, Tomomi; Tsutsui, Hiroyuki; Sunagawa, Kenji

doi:10.1093/ajh/hpx062

Cited by 11 publications

(8 citation statements)

References 34 publications

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“…The 24 h urinary samples were collected using metabolic cages, as described previously (Fujii et al, 2017). The 24 h urinary samples were collected using metabolic cages, as described previously (Fujii et al, 2017).…”

Section: Parameters Of Sympathetic Nerve Activitymentioning

confidence: 99%

“…The 24 h urinary noradrenaline excretion (U-NA) and plasma noradrenaline concentration (P-NA) were evaluated as indexes of SNA. The 24 h urinary samples were collected using metabolic cages, as described previously (Fujii et al, 2017). The U-NA was measured by high-performance liquid chromatography at a commercial laboratory (SRL, Tokyo, Japan).…”

Section: Parameters Of Sympathetic Nerve Activitymentioning

confidence: 99%

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Suppressed baroreflex peripheral arc overwhelms augmented neural arc and incapacitates baroreflex function in rats with pulmonary arterial hypertension

Shinoda

Saku

Oga

et al. 2019

Experimental Physiology

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New Findings What is the central question of this study?The impact of pulmonary arterial hypertension on open‐loop baroreflex function, which determines how powerfully and rapidly the baroreflex operates to regulate arterial pressure, remains poorly understood. What is the main finding and its importance?The gain of the baroreflex total arc, indicating the baroreflex pressure‐stabilizing function, is markedly attenuated in rats with monocrotaline‐induced pulmonary arterial hypertension. This is caused by a rightward shift of the baroreflex neural arc and a downward shift of the peripheral arc. These findings contribute greatly to our understanding of arterial pressure regulation by the sympathetic nervous system in pulmonary arterial hypertension. Abstract Sympathoexcitation has been documented in patients with established pulmonary arterial hypertension (PAH). Although the arterial baroreflex is the main negative feedback regulator of sympathetic nerve activity (SNA), the way in which PAH impacts baroreflex function remains poorly understood. In this study, we conducted baroreflex open‐loop analysis in a rat model of PAH. Sprague–Dawley rats were injected with monocrotaline (MCT) s.c. to induce PAH (60 mg kg−1; n = 11) or saline as a control group (CTL; n = 8). At 3.5 weeks after MCT injection, bilateral carotid sinuses were isolated, and intrasinus pressure (CSP) was controlled while SNA at the coeliac ganglia and arterial pressure (AP) were recorded. To examine the static baroreflex function, CSP was increased stepwise while steady‐state AP (total arc) and SNA (neural arc) responses to CSP and the AP response to SNA (peripheral arc) were measured. Monocrotaline significantly decreased the static gain of the baroreflex total arc at the operating AP compared with CTL (−0.80 ± 0.31 versus −0.22 ± 0.22, P < 0.05). Given that MCT markedly increased plasma noradrenaline, an index of SNA, by approximately 3.6‐fold compared with CTL, calibrating SNA by plasma noradrenaline revealed that MCT shifted the neural arc to a higher SNA level and shifted the peripheral arc downwards. Monocrotaline also decreased the dynamic gain of the baroreflex total arc (−0.79 ± 0.16 versus −0.35 ± 0.17, P < 0.05), while the corner frequencies that reflect the speed of the baroreflex remained unchanged (0.06 ± 0.02 versus 0.08 ± 0.02 Hz, n.s.). In rats with MCT‐induced PAH, the suppressed baroreflex peripheral arc overwhelms the augmented neural arc and, in turn, attenuates the gain of the total arc, which determines the pressure‐stabilizing capacity of the baroreflex.

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Section: Parameters Of Sympathetic Nerve Activitymentioning

confidence: 99%

Section: Parameters Of Sympathetic Nerve Activitymentioning

confidence: 99%

Suppressed baroreflex peripheral arc overwhelms augmented neural arc and incapacitates baroreflex function in rats with pulmonary arterial hypertension

Shinoda

Saku

Oga

et al. 2019

Experimental Physiology

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“…2020, 21, 4893 2 of 14 followed by hypertension. The CB is involved in the origin of hypertension and the functional elimination of CB after denervation or ablation prevents the development of hypertension [6][7][8][9][10]. The hyperactivity of the sympathetic system seems to be the link between CB and hypertension [11].…”

Section: Introductionmentioning

confidence: 99%

“…It is currently accepted that chronic intermittent hypoxia (CIH) produces carotid body (CB) sensitization generating an increased input to the brain stem which originates sympathetic hyperactivity, followed by hypertension. The CB is involved in the origin of hypertension and the functional elimination of CB after denervation or ablation prevents the development of hypertension [ 6 , 7 , 8 , 9 , 10 ]. The hyperactivity of the sympathetic system seems to be the link between CB and hypertension [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Peripheral Dopamine 2-Receptor Antagonist Reverses Hypertension in a Chronic Intermittent Hypoxia Rat Model

Olea

Docio

Quintero

et al. 2020

IJMS

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The sleep apnea-hypopnea syndrome (SAHS) involves periods of intermittent hypoxia, experimentally reproduced by exposing animal models to oscillatory PO2 patterns. In both situations, chronic intermittent hypoxia (CIH) exposure produces carotid body (CB) hyperactivation generating an increased input to the brainstem which originates sympathetic hyperactivity, followed by hypertension that is abolished by CB denervation. CB has dopamine (DA) receptors in chemoreceptor cells acting as DA-2 autoreceptors. The aim was to check if blocking DA-2 receptors could decrease the CB hypersensitivity produced by CIH, minimizing CIH-related effects. Domperidone (DOM), a selective peripheral DA-2 receptor antagonist that does not cross the blood-brain barrier, was used to examine its effect on CIH (30 days) exposed rats. Arterial pressure, CB secretory activity and whole-body plethysmography were measured. DOM, acute or chronically administered during the last 15 days of CIH, reversed the hypertension produced by CIH, an analogous effect to that obtained with CB denervation. DOM marginally decreased blood pressure in control animals and did not affect hypoxic ventilatory response in control or CIH animals. No adverse effects were observed. DOM, used as gastrokinetic and antiemetic drug, could be a therapeutic opportunity for hypertension in SAHS patients’ resistant to standard treatments.

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“…CB, located at the bifurcation region of each common carotid artery, is the main peripheral arterial chemoreceptor that senses changes in the levels of oxygen, pH and carbon dioxide in the body 10,11 . A recent study with an animal model of hypertensive HF has shown that CB denervation markedly improved the survival in rats 12 . In fact, single or bilateral removal of CB in clinical studies with >15,000 patients has been reported in the literature with no adverse effects 9 .…”

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confidence: 99%

Precision Targeted Ablation of Fine Neurovascular Structures In Vivo Using Dual-mode Ultrasound Arrays

Aravalli¹,

Helden

Liu³

et al. 2020

Sci Rep

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carotid bodies (cBs) are chemoreceptors that monitor and register changes in the blood, including the levels of oxygen, carbon dioxide, and pH, and regulate breathing. enhanced activity of cBs was shown to correlate with a significant elevation in the blood pressure of patients with hypertension. CB removal or denervation were previously shown to reduce hypertension. Here we demonstrate the feasibility of a dual-mode ultrasound array (DMUA) system to safely ablate the cB in vivo in a spontaneously hypertensive rat (SHR) model of hypertension. DMUA imaging was used for guiding and monitoring focused ultrasound (FUS) energy delivered to the target region. In particular, 3D imaging was used to identify the carotid bifurcation for targeting the cBs. intermittent, high frame rate imaging during image-guided fUS (igfUS) delivery was used for monitoring the lesion formation. DMUA imaging provided feedback for closed-loop control (cLc) of the lesion formation process to avoid overexposure. The procedure was tolerated well in over 100 SHR and normotensive rats that received unilateral and bilateral treatments. the measured mean arterial pressure (MAp) exhibited measurable deviation from baseline 2-4 weeks post IgFUS treatment. The results suggest that the direct unilateral FUS treatment of the CB might be sufficient to reduce the blood pressure in hypertensive rats and justify further investigation in large animals and eventually in human patients.

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Carotid Body Denervation Markedly Improves Survival in Rats With Hypertensive Heart Failure

Abstract: CBD attenuated the progression of hypertension and worsening of heart failure possibly through sympathoinhibition, and markedly improved survival in a rat model of hypertensive heart failure.

Cited by 11 publications

References 34 publications

Suppressed baroreflex peripheral arc overwhelms augmented neural arc and incapacitates baroreflex function in rats with pulmonary arterial hypertension

Suppressed baroreflex peripheral arc overwhelms augmented neural arc and incapacitates baroreflex function in rats with pulmonary arterial hypertension

Peripheral Dopamine 2-Receptor Antagonist Reverses Hypertension in a Chronic Intermittent Hypoxia Rat Model

Precision Targeted Ablation of Fine Neurovascular Structures In Vivo Using Dual-mode Ultrasound Arrays

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