Shuji Shimizu

National Cerebral and Cardiovascular Center, Ōsaka, Ōsaka, Japan

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Publications (63)130.26 Total impact

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    ABSTRACT: Arterial baroreceptors can be divided into two categories dependent on whether their axons are myelinated (A-fiber) or unmyelinated (C-fiber). We investigated the effect of periaxonal resiniferatoxin (RTX), a blocker of C-fiber baroreceptor activity, on the open-loop static characteristics of the arterial baroreflex. The baroreceptor region of the right aortic depressor nerve was isolated, and intra-baroreceptor region pressure (BRP) was changed from 60 to 180mmHg in 10 anesthetized Sprague-Dawley rats. Open-loop static characteristics of the neural arc from BRP to efferent sympathetic nerve activity (SNA), peripheral arc from SNA to arterial pressure (AP), and total reflex arc from BRP to AP were estimated. Although blocking C-fiber activity with RTX resulted in a lower response range (33.7±4.6% and 49.4±4.8%, P<0.01) and higher minimum SNA (78.0±4.7% and 53.6±5.0%, P<0.001) of the steady-state neural arc, the peak SNA response to BRP was greater at a BRP of 160mmHg (-37.87±5.83% and -26.28±4.90%, P=0.01). RTX also resulted in a lower response range (27.8±5.0mmHg and 40.9±5.2mmHg, P<0.01) and higher minimum AP (92.4±4.7mmHg and 79.1±4.9mmHg, P<0.001) of the total reflex arc. Despite these changes, the maximum slope of the neural arc and the maximum gain of the total reflex arc did not differ significantly after RTX. These data suggest that A-fiber baroreceptors can regulate AP and maintain the maximum gain when systemic AP is around the normal operating range. In contrast, C-fiber baroreceptors are critically important for reductions in SNA and AP when systemic AP is raised above the normal operating range. Copyright © 2015 Elsevier B.V. All rights reserved.
    Autonomic neuroscience: basic & clinical 05/2015; DOI:10.1016/j.autneu.2015.05.008 · 1.37 Impact Factor
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    ABSTRACT: Although oxidative redox signaling affects arterial pressure (AP) regulation via modulation of vascular tone and sympathetic nerve activity (SNA), it remains unknown which effect plays a dominant role in the determination of AP in vivo. Open-loop systems analysis of the carotid sinus baroreflex was conducted to separately quantify characteristics of the neural arc from baroreceptor pressure input to SNA and the peripheral arc from SNA to AP in normotensive Wistar-Kyoto (WKY, n = 8) and spontaneously hypertensive rats (SHR, n = 8). Responses in SNA and AP to a staircase-wise increase in carotid sinus pressure were examined before and during intravenous administration of the membrane permeable superoxide dismutase mimetic tempol (30 mg/kg bolus followed by 30 mg·kg(-1)·h(-1)). Two-way analysis of variance indicated that tempol significantly decreased the response range of SNA (from 89.1±2.4% to 60.7±2.5% in WKY, and from 77.5±3.2% to 56.9±7.3% in SHR, P < 0.001) without affecting the lower plateau of SNA (from 12.5±2.4% to 9.5±2.5% in WKY, and from 28.8±2.8% to 30.4±5.7% in SHR, P = 0.800) in the neural arc. While tempol did not affect the peripheral arc characteristics in WKY, it yielded a downward change in the regression line of AP versus SNA in SHR. In conclusion, oxidative redox signaling plays an important role, not only in the pathological AP elevation, but also in the baroreflex-mediated physiological AP regulation. The effect of modulating oxidative redox signaling on the peripheral arc contributed to the determination of AP in SHR but not in WKY. Copyright © 2014, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology.
    AJP Regulatory Integrative and Comparative Physiology 03/2015; 308(11):ajpregu.00525.2014. DOI:10.1152/ajpregu.00525.2014 · 3.53 Impact Factor
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    ABSTRACT: There is ongoing controversy over whether neural or peripheral factors are the predominant cause of hypertension. The closed-loop negative feedback operation of the arterial baroreflex hampers understanding of how arterial pressure (AP) is determined through the interaction between neural and peripheral factors.Methods and Results:A novel analysis of an isolated open-loop baroreceptor preparation to examine sympathetic nervous activity (SNA) and AP responses to changes in carotid sinus pressure (CSP) in adult spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) was conducted. In the neural arc (CSP-SNA relationship), the midpoint pressure (128.9±3.8 vs. 157.9±8.1 mmHg, P<0.001) and the response range of SNA to CSP (90.5±3.7 vs. 115.4±7.6%/mmHg, P=0.011) were higher in SHR. In the peripheral arc (SNA-AP relationship), slope and intercept did not differ. A baroreflex equilibrium diagram was obtained by depicting neural and peripheral arcs in a pressure-SNA plane with rescaled SNA (% in WKY). The operating-point AP (111.3±4.4 vs. 145.9±5.2 mmHg, P<0.001) and SNA (90.8±3.2 vs. 125.1±6.9% in WKY, P<0.001) were shifted towards a higher level in SHR. The shift of the neural arc towards a higher SNA range indicated a predominant contribution to baroreflex resetting in SHR. Notwithstanding the resetting, the carotid sinus baroreflex in SHR preserved an ability to reduce AP if activated with a high enough pressure. (Circ J 2015; 79: 592-599).
    Circulation Journal 02/2015; 79(3):592-9. DOI:10.1253/circj.CJ-14-1013 · 3.69 Impact Factor
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    ABSTRACT: To assess the acute effects of intravenous azelnidipine, a third-generation L-type calcium channel blocker, on sympathetic outflow from the central nervous system and to compare the effects of intravenous azelnidipine with those of intravenous nifedipine. In anesthetized Wistar Kyoto rats, carotid sinus baroreceptor regions were isolated. Changes in sympathetic nerve activity (SNA) and arterial pressure (AP) in response to a stepwise pressure input were examined before and during intravenous nifedipine or azelnidipine (for each: 100 μg/kg bolus followed by 300 μg/kg/h infusion, n = 6). Nifedipine significantly reduced the range of the AP response from 76.8 ± 7.4 to 45.4 ± 7.0 mmHg (P < 0.01) but did not affect the range of the SNA response (from 84.4 ± 5.1 to 85.9 ± 10.2%) or the SNA maximum gain (from 2.26 ± 0.28 to 2.35 ± 0.55%/mmHg). Similarly, azelnidipine significantly reduced the range of the AP response from 62.4 ± 3.9 to 31.4 ± 4.1 mmHg (P < 0.01) but did not affect the range of the SNA response (from 71.2 ± 5.5 to 74.9 ± 7.2%) or the SNA maximum gain (from 1.64 ± 0.17 to 2.08 ± 0.26%/mmHg). A depressor dose of nifedipine or azelnidipine does not have an acute sympathoinhibitory effect in normotensive Wistar Kyoto rats even when the level of SNA was varied over the entire operating range of the carotid sinus baroreflex. Copyright © 2015. Published by Elsevier Inc.
    Life Sciences 02/2015; 126. DOI:10.1016/j.lfs.2015.01.024 · 2.30 Impact Factor
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    ABSTRACT: Decreased carotid arterial compliance has been reported in obese subjects and animals. Carotid baroreceptors are located at the bifurcation of the common carotid artery, and respond to distension of the arterial wall, suggesting that higher pressure is required to obtain the same distension in obese subjects and animals. A hyperosmotic NaCl solution induces circulatory volume expansion and arterial pressure (AP) increase, which reflexively augment renal excretion. Thus, we hypothesized that sodium regulation via the baroreflex might be impaired in response to chronic hyperosmotic NaCl infusion in rats fed a high-fat diet. To examine this hypothesis, we used rats fed a high-fat (Fat) or normal (NFD) diet, and measured mean AP, water and sodium balance, and renal function in response to chronic infusion of hyperosmotic NaCl solution via a venous catheter. Furthermore, we examined arterial baroreflex characteristics with static open-loop analysis and distensibility of the common carotid artery. Significant positive water and sodium balance was observed on the 1st day of 9% NaCl infusion; however, this disappeared by the 2nd day in Fat rats. Mean AP was significantly higher during 9% NaCl infusion in Fat rats compared with NFD rats. In the open-loop analysis of carotid sinus baroreflex, a rightward shift of the neural arc was observed in Fat rats compared with NFD rats. Furthermore, distensibility of the common carotid artery was significantly reduced in Fat rats. These results indicate that a reduced baroreceptor distensibility-induced rightward shift of the neural arc might contribute to impairment of sodium regulation in Fat rats. Copyright © 2014, American Journal of Physiology - Heart and Circulatory Physiology.
    AJP Heart and Circulatory Physiology 02/2015; 308(8):ajpheart.00697.2014. DOI:10.1152/ajpheart.00697.2014 · 4.01 Impact Factor
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    ABSTRACT: A baroreflex equilibrium diagram describes the relation between input pressure and sympathetic nerve activity (SNA) and that between SNA and arterial pressure (AP). To calibrate the SNA axis (abscissa) of the baroreflex equilibrium diagram, the AP response to intravenous bolus injections of phenylephrine (0.2-50 μg/kg) or norepinephrine (NE, 0.02-5 μg/kg) was examined in normal control rats (NC, n = 9) and rats with chronic heart failure (CHF, n = 6). The maximum slope of the dose-effect curve was significantly smaller in the CHF group than in the NC group (57.3 ± 5.2 vs 80.9 ± 6.3 mmHg/decade for phenylephrine, 60.2 ± 7.8 vs 80.4 ± 5.9 mmHg/decade for NE; P < 0.01). The CHF/NC ratio of the maximum slope was used to calibrate SNA. While the calibrated baroreflex equilibrium diagram showed increased maximum SNA and operating-point SNA in CHF rats compared with NC rats, the magnitude of increase was smaller than that expected from the excess plasma NE concentration in CHF rats. Plasma NE concentration in the CHF group could be disproportionally high relative to SNA.
    02/2015; 9(Suppl 1):1-9. DOI:10.4137/CMC.S18759
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    ABSTRACT: A hybrid procedure combining bilateral pulmonary artery banding with ductal stenting has recently been used as stage I palliation for hypoplastic left heart syndrome. However, the advantage of the hybrid procedure over the Norwood procedure on ventricular energetics remains unclear. To clarify this, we performed a computational analysis with a combination of time-varying elastance chamber model and modified three-element Windkessel vascular model. Although mean pulmonary artery (PA) pressure, pulmonary flow, and oxygen saturation were almost equivalent with the Norwood procedure, the hybrid procedure delivered higher systolic and lower diastolic systemic arterial pressures compared to the Norwood procedure with right ventricle (RV) to PA shunt. As a result, the hybrid procedure yielded increased systolic pressure-volume area and impaired mechanical efficiency. Therefore, the hybrid procedure has probably no advantage on ventricular energetics compared to the Norwood procedure with a RV-PA shunt.
    Heart and Vessels 11/2014; DOI:10.1007/s00380-014-0604-6 · 2.11 Impact Factor
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    ABSTRACT: An α2A-adrenergic agonist guanfacine improves autonomic imbalance in attention-deficit hyperactivity disorder, suggesting that it may be useful to correct autonomic imbalance in chronic heart failure (CHF) patients. To investigate the effects of guanfacine on cardiac autonomic nerve activities, a microdialysis technique was applied to anesthetized rabbit heart. Acetylcholine (ACh) and norepinephrine (NE) concentrations in atrial dialysates were measured as indices of cardiac autonomic nerve activities. Guanfacine at a dose of 100μg/kg significantly decreased heart rate and increased dialysate ACh concentration without decreasing sympathetic NE release. Guanfacine may be useful for vagal activation therapy in CHF patients. Copyright © 2014 Elsevier B.V. All rights reserved.
    Autonomic neuroscience: basic & clinical 11/2014; 187. DOI:10.1016/j.autneu.2014.11.010 · 1.37 Impact Factor
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    ABSTRACT: Arterial pressure (AP) elevates as a logarithmic function of exogenously administered dose of norepinephrine (NE). In contrast, AP is nearly linearly correlated with efferent sympathetic nerve activity (SNA) during acute baroreflex intervention. The present study aimed at quantifying the relationship between SNA and plasma NE concentration during acute baroreflex intervention. Carotid sinus regions were isolated from systemic circulation in five Wistar Kyoto rats, and carotid sinus pressure was changed among 60, 100, 120, 140, and 180mmHg every 2min. Arterial blood (0.2ml) was obtained at each pressure level for plasma NE measurement. Maximum AP and minimum AP were 153.34±6.28 and 67.31±4.92mmHg, respectively, in response to pressure perturbation. Plasma NE correlated linearly with SNA for individual animal data (slope: 0.957±0.090pg·ml(-1)·%(-1), intercept: 46.57±7.22pg/ml, r(2): ranged from 0.923 to 0.992) and also for group averaged data (NE=0.956×SNA+47.97, r(2)=0.982). Blockade of neuronal NE uptake by intravenous desipramine (1mg/kg) administration increased the slope (2.966±0.686pg·ml(-1)·%(-1), P<0.05) and the intercept (168.73±28.53pg/ml, P<0.01) of the plasma NE-SNA relationship. These results indicate that the relationship between SNA and plasma NE concentration was nearly linear within the normal physiological range of acute baroreflex control of AP. While plasma NE concentration can reflect changes in SNA, it may also overestimate the sympathetic outflow from the central nervous system when neuronal NE uptake is impaired systemically. Copyright © 2014 Elsevier B.V. All rights reserved.
    Autonomic neuroscience: basic & clinical 10/2014; 186C:62-68. DOI:10.1016/j.autneu.2014.10.016 · 1.37 Impact Factor
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    ABSTRACT: To examine the effects of cariporide, a Na(+)/H(+) exchanger-1 inhibitor, on cardiac norepinephrine (NE) and myoglobin releases during myocardial ischemia/reperfusion by applying a microdialysis technique to the rabbit heart.
    Life Sciences 08/2014; 114(2). DOI:10.1016/j.lfs.2014.08.008 · 2.30 Impact Factor
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    ABSTRACT: In elderly patients, open surgery for patent ductus arteriosus (PDA) is more difficult than that in children and often requires a cardiopulmonary bypass. We report the case of a 67-year-old patient with a PDA that was successfully treated with thoracic endovascular aortic repair (TEVAR). The patient was diagnosed with congestive heart failure (ejection fraction, 36 %) and PDA (9.7 mm in diameter). TEVAR was successfully performed to exclude the PDA. After TEVAR, the patient's heart failure was well controlled by diuretics. TEVAR may be a good alternative to open surgery.
    General Thoracic and Cardiovascular Surgery 07/2014; DOI:10.1007/s11748-014-0457-z
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    ABSTRACT: Arterial aneurysm rupture is one of the most critical complications in patients with vascular-type Ehlers–Danlos syndrome (vEDS). Here, we report a case of recurrent aneurysm rupture successfully treated by endovascular embolization. A 38-year old woman who underwent brachial artery ligation for a ruptured aneurysm was diagnosed postoperatively with vEDS. Impending rupture of a collateral artery aneurysm was encountered 5 months after the initial open surgery. Endovascular embolization with a liquid embolic agent was successfully performed. Given that arterial rupture can occur repeatedly in patients with vEDS, careful life-long follow-up is necessary.
    Interactive Cardiovascular and Thoracic Surgery 07/2014; 19(4). DOI:10.1093/icvts/ivu208 · 1.11 Impact Factor
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    ABSTRACT: To identify the contribution of myelinated (A-fibre) and unmyelinated (C-fibre) baroreceptor central pathways to the baroreflex control of sympathetic nerve activity and arterial pressure. Two binary white noise stimulation protocols were used to electrically stimulate the aortic depressor nerve and activate reflex responses from either A-fibre (3V, 20-100Hz) or C-fibre (20V, 0-10Hz) baroreceptor in anesthetized Sprague-Dawley rats (n=10). Transfer function analysis was performed between stimulation and sympathetic nerve activity (central arc), sympathetic nerve activity and arterial pressure (peripheral arc), and stimulation and arterial pressure (Stim-AP arc). The central arc transfer function from nerve stimulation to splanchnic sympathetic nerve activity displayed derivative characteristics for both stimulation protocols. However, the modeled steady-state gain (0.28±0.04 vs. 4.01±0.2 %·Hz(-1), P<0.001) and coherence at 0.01Hz (0.44±0.05 vs. 0.81±0.03, P<0.05) were significantly lower for A-fibre stimulation compared with C-fibre stimulation. The slope of the dynamic gain was higher for A-fibre stimulation (14.82±1.02 vs. 7.21±0.79dB·decade(-1), P<0.001). The steady-state gain of the Stim-AP arc was also significantly lower for A-fibre stimulation compared with C-fibre stimulation (0.23±0.05 vs. 3.05±0.31mmHg·Hz(-1), P<0.001). These data indicate that the A-fibre central pathway contributes to high frequency arterial pressure regulation and the C-fibre central pathway provides more sustained changes in sympathetic nerve activity and arterial pressure. A sustained reduction in arterial pressure from electrical stimulation of arterial baroreceptor afferents is likely mediated through the C-fibre central pathway.
    Life sciences 04/2014; 106(1). DOI:10.1016/j.lfs.2014.04.016 · 2.30 Impact Factor
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    ABSTRACT: Background: To identify a pharmacological agent that can selectively activate cardiac vagus nerve for potential use in vagal activation therapy against heart failure, the effects of medetomidine on autonomic nerve activities in both the heart and stomach were examined. Methods and Results: In anesthetized rabbits, microdialysis probes were implanted into both the right atrial and gastric walls. Dialysate acetylcholine (ACh) and norepinephrine (NE) concentrations were measured by high-performance liquid chromatography. First, the effects of 100μg/kg of intravenous medetomidine on vagal ACh and sympathetic NE releases were examined. Medetomidine significantly increased cardiac ACh release (4.7±1.1 to 7.8±0.9nmol/L, P<0.05), but suppressed gastric ACh release (8.0±2.6 to 3.5±1.5nmol/L, P<0.01). In contrast, medetomidine suppressed both cardiac and gastric NE releases. Second, the effects of medetomidine on ACh releases induced by electrical vagus nerve stimulation (VNS; 10Hz) were examined. Electrical VNS significantly increased both cardiac (6.7±1.2 to 14.8±1.8nmol/L, P<0.01) and gastric (3.8±0.8 to 181.3±65.6nmol/L, P<0.01) ACh releases. Medetomidine did not alter the VNS-induced increases in ACh release. Conclusions: Medetomidine suppresses both cardiac and gastric sympathetic nerve activities. In contrast, medetomidine activates cardiac vagus nerve but inhibits gastric vagal activity. Medetomidine might be one of the potential pharmacological agents for vagal activation therapy against heart failure without the risk of gastric adverse effects.
    Circulation Journal 04/2014; 78(6). DOI:10.1253/circj.CJ-13-1456 · 3.69 Impact Factor
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    ABSTRACT: We tested whether 6-week vagal stimulation (VS) treatment improved open-loop baroreflex function in rats after myocardial infarction (MI). The following three groups of Sprague-Dawley rats were examined: normal control (NC, n = 9), MI with no treatment (MI-NT, n = 8) and MI treated with VS (MI-VS, n = 7). Under anesthesia, a stepwise input ranging from 60 to 180 mmHg was imposed on isolated carotid sinus baroreceptor regions, while the responses in splanchnic sympathetic nerve activity (SNA) and arterial pressure (AP) were measured. The response range of percent SNA was greater in the MI-VS than in the MI-NT group (63.8 ± 4.9% vs. 33.1 ± 3.8%, P < 0.01). The slope of the AP response to percent SNA was not different between the MI-VS and MI-NT groups (0.611 ± 0.076 vs. 0.781 ± 0.057 mmHg/%). The difference in the response range of AP between the MI-VS and MI-NT groups did not reach statistical significance (40.7 ± 6.2 vs. 26.4 ± 3.5 mmHg). In conclusion, the 6-week VS treatment significantly improved the baroreflex control of SNA, but the effect was limited for the baroreflex total-loop function due to the lack of significant improvement in the AP response to percent SNA.
    Journal of Applied Physiology 03/2014; 116(10). DOI:10.1152/japplphysiol.00140.2014 · 3.43 Impact Factor
  • Koji Nakanishi · Ryoji Watanabe · Shuji Shimizu · Mikizo Nakai
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    ABSTRACT: Non-anastomotic graft rupture is a rare but critical complication after abdominal aortic aneurysm (AAA) repair. Therefore, identifying the rupture sites is important to perform endovascular stent grafting. A 78-year old man who had undergone Y-grafting for infrarenal AAA before 17 years was referred to our hospital with the complaints of abdominal pain. Computed tomography revealed acute pancreatitis and an enlargement around the grafted abdominal aorta. Contrast-enhanced ultrasonography revealed an extravazation from the graft body 1.5 cm distal to the proximal anastomosis, and endovascular stent grafting was successfully performed. Contrast-enhanced ultrasonography might be useful in detecting the graft rupture.
    Interactive Cardiovascular and Thoracic Surgery 11/2013; 18(2). DOI:10.1093/icvts/ivt485 · 1.11 Impact Factor
  • Masaru Sugimachi · Toru Kawada · Meihua Li · Can Zheng · Shuji Shimizu
    Journal of Cardiac Failure 10/2013; 19(10):S126. DOI:10.1016/j.cardfail.2013.08.122 · 3.07 Impact Factor
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    ABSTRACT: Dynamic characteristics of arterial pressure (AP) regulation are important components in our understanding of rapid AP restoration by the arterial baroreflex system. The present study examined the effects of an L-type Ca(2+) channel blocker nifedipine on baroreflex-mediated dynamic AP regulation. In anesthetized and vagotomized rats, carotid sinus pressure was externally perturbed using a Gaussian white noise signal, and the neural arc transfer function from pressure input to efferent sympathetic nerve activity (SNA) and the peripheral arc transfer function from SNA to AP were identified. The peripheral arc transfer function approximated a second-order low-pass filter with pure dead time. Intravenous administration of nifedipine significantly decreased the steady-state gain and increased the damping ratio of the peripheral arc without affecting the dynamic characteristics of the neural arc. When the step response of AP was calculated based on the peripheral arc transfer function alone, nifedipine prolonged 80% rise time by 26%. When the closed-loop AP response was simulated based on both the neural arc and peripheral arc transfer functions and the dynamic gain of the baroreflex total loop was assumed to be 2.0, nifedipine prolonged 80% recovery time by 107%. In conclusion, L-type Ca(2+) channel blockade may compromise the baroreflex-mediated AP control not only in the magnitude but also in the speed of AP restoration.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 07/2013; 2013:3805-3808. DOI:10.1109/EMBC.2013.6610373
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    ABSTRACT: To examine whether sympathetic afferent stimulation (SAS) inhibits central vagal activation induced by α2-adrenergic stimulation. In anaesthetized Wistar-Kyoto rats, a cardiac microdialysis technique was applied to the left ventricle, and the effect of α2-adrenergic stimulation by medetomidine on myocardial interstitial acetylcholine (ACh) levels was examined in the absence (n = 6) or the presence (n = 6) of SAS delivered from the left stellate ganglion. The effect of electrical vagal efferent stimulation on myocardial interstitial ACh release was also examined in the absence or the presence of SAS (n = 6). Intravenous medetomidine (0.1 mg kg−1) significantly increased myocardial interstitial ACh levels in the absence of SAS (from 1.95 ± 0.79 to 3.36 ± 1.61 nm, P < 0.05), but not in the presence of SAS (from 1.67 ± 0.67 to 2.01 ± 0.78 nm). In contrast, electrical vagal nerve stimulation increased myocardial interstitial ACh level to the same degree regardless of SAS (from 1.66 ± 0.16 to 3.93 ± 0.72 nm without SAS vs. 4.05 ± 0.89 nm with SAS). Sympathetic afferent stimulation inhibited medetomidine-induced ACh release, but not electrical stimulation-induced ACh release, suggesting that SAS inhibited medetomidine-induced vagal activation via central mechanisms. While central vagal activation by α2-adrenergic agonists could be an alternative to electrical vagal activation, blocking sympathetic afferent input may be important to increase the efficacy of α2-adrenergic agonists in enhancing vagal nerve activity.
    Acta Physiologica 05/2013; 209(1). DOI:10.1111/apha.12123 · 4.25 Impact Factor
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    ABSTRACT: AIMS: Cilnidipine is a unique Ca(2+) channel blocker that inhibits both L-type and N-type Ca(2+) channels. The present study aimed to assess the effects of intravenous cilnidipine on sympathetic outflow and sympathetic arterial pressure (AP) and heart rate (HR) regulations. MAIN METHODS: Carotid sinus baroreceptor regions were isolated from the systemic circulation in anesthetized and vagotomized Wistar Kyoto rats. Changes in efferent sympathetic nerve activity (SNA), AP and HR in response to a stepwise input of carotid sinus pressure were examined before and during intravenous cilnidipine administration (30 μg/kg bolus + 100 μg kg(-1)h(-1) infusion, n = 6). KEY FINDINGS: Cilnidipine significantly reduced the AP response range (from 68.0 ± 10.2 to 34.6 ± 4.1 mmHg, P = 0.007) but did not affect the SNA response range (from 90.4 ± 10.3 to 84.7 ± 9.5%, P = 0.297) or the HR response range (from 50.4 ± 10.1 to 48.1 ± 6.2 beats/min, P = 0.719). SIGNIFICANCE: Cilnidipine, at a depressor dose used in the present study, does not acutely suppress sympathetic outflow from the central nervous system. Also, it spared the sympathetic HR response, suggesting that N-type Ca(2+) channel blocking action at the cardiac sympathetic nerve endings may be a modest one.
    Life sciences 05/2013; 92(24-26). DOI:10.1016/j.lfs.2013.05.004 · 2.30 Impact Factor