Aortic depressor nerve stimulation does not impede the dynamic characteristics of the carotid sinus baroreflex in normotensive or spontaneously hypertensive rats

Kawada, Toru; Turner, Michael J.; Shimizu, Shuji; Fukumitsu, Masafumi; Kamiya, Atsunori; Sugimachi, Masaru

doi:10.1152/ajpregu.00530.2016

Cited by 4 publications

(10 citation statements)

References 31 publications

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“…These results indicate that electrical stimulation of the ADN does not significantly impede dynamic characteristics of the aortic baroreflex mediated by the stimulated ADN. The results are qualitatively similar to those observed in a previous study in which the tonic ADN stimulation did not significantly affect dynamic characteristics of the carotid sinus baroreflex (18). Nevertheless, the present study (Fig.…”

Section: Discussionsupporting

confidence: 93%

“…Because of technical difficulty in selectively stimulating the baroreceptor fibers in the carotid sinus nerve (9), we examined the aortic baroreflex mediated by the right ADN. In contrast to the previous study (18), an interaction between the electrical stimulation and pressure inputs could occur peripherally at afferent fibers (Fig. 1B) although a central interaction may also occur after the afferent signals reach the brain stem.…”

Section: Introductioncontrasting

confidence: 92%

“…Schemata showing possible interaction between electrical stimulation and pressure inputs. A: interaction was examined between 2 baroreflex systems in our previous study (18). The site of a possible interaction is central.…”

Section: Methodsmentioning

confidence: 99%

“…When the arterial baroreflex system is divided into the neural arc from a pressure input to efferent sympathetic nerve activity (SNA) and the peripheral arc from SNA to AP, the fast neural arc compensates for the slow peripheral arc to achieve the quick and stable recovery of AP against pressure perturbations (14). In a previous study, we electrically stimulated the left aortic depressor nerve (ADN) while estimating the dynamic characteristics of the carotid sinus baroreflex in response to pressure inputs (18) to examine a possible interaction between electrical stimulation and pressure inputs in the brain stem, where the signals from two baroreflex systems are integrated (Fig. 1A).…”

Section: Introductionmentioning

confidence: 99%

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Tonic aortic depressor nerve stimulation does not impede baroreflex dynamic characteristics concomitantly mediated by the stimulated nerve

Kawada

Turner

Shimizu

et al. 2018

American Journal of Physiology-Regulatory, Integrative and Comp

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Although electrical activation of the carotid sinus baroreflex (baroreflex activation therapy) is being explored as a device therapy for resistant hypertension, possible effects on baroreflex dynamic characteristics of interaction between electrical stimulation and pressure inputs are not fully elucidated. To examine whether the electrical stimulation of the baroreceptor afferent nerve impedes normal short-term arterial pressure (AP) regulation mediated by the stimulated nerve, we electrically stimulated the right aortic depressor nerve (ADN) while estimating the baroreflex dynamic characteristics by imposing pressure inputs to the isolated baroreceptor region of the right ADN in nine anesthetized rats. A Gaussian white noise signal with a mean of 120 mmHg and standard deviation of 20 mmHg was used for the pressure perturbation. A tonic ADN stimulation (2 or 5 Hz, 10 V, 0.1-ms pulse width) decreased mean sympathetic nerve activity (367.0 ± 70.9 vs. 247.3 ± 47.2 arbitrary units, P < 0.01) and mean AP (98.4 ± 7.8 vs. 89.2 ± 4.5 mmHg, P < 0.01) during dynamic pressure perturbation. The ADN stimulation did not affect the slope of dynamic gain in the neural arc transfer function from pressure perturbation to sympathetic nerve activity (16.9 ± 1.0 vs. 14.7 ± 1.6 dB/decade, not significant). These results indicate that electrical stimulation of the baroreceptor afferent nerve does not significantly impede the dynamic characteristics of the arterial baroreflex concomitantly mediated by the stimulated nerve. Short-term AP regulation by the arterial baroreflex may be preserved during the baroreflex activation therapy.

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Section: Discussionsupporting

confidence: 93%

Section: Introductioncontrasting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tonic aortic depressor nerve stimulation does not impede baroreflex dynamic characteristics concomitantly mediated by the stimulated nerve

Kawada

Turner

Shimizu

et al. 2018

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Another clinical study suggests that an arti cial input from one baroreceptor area decreases AP in hypertensive patients without a negative impact on physiological barore ex regulation [17]. In anesthetized rats, tonic electrical stimulation of the aortic depressor nerve does not impede the dynamic characteristics of the carotid sinus barore ex [18]. Taken these results together, it appears that the input from one baroreceptor area is capable of controlling SNA independent of the input from the other baroreceptor area unless the inhibitory effect on SNA is saturated.…”

Section: Application To the Barore Ex Systemmentioning

confidence: 99%

Linear and Nonlinear Analysis of the Carotid Sinus Baroreflex Dynamic Characteristics

Kawada

Mukkamala

Sugimachi

2019

ABE

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The arterial barore ex system is an important negative feedback system that controls arterial pressure (AP) within a normal range during daily activities. We have analyzed this system in anesthetized animals. Several issues need to be considered: the presence of physiological and measurement noises that interfere with the system identi cation, the closed-loop nature of the arterial barore ex system, the existence of parallel feedback systems that may modify the system responses, and the presence of nonlinear responses. We opened the negative feedback loop by surgically isolating the carotid sinus baroreceptor regions from the systemic circulation. We eliminated the effects from parallel feedback systems by sectioning the aortic depressor and vagal nerves. We used a white noise approach to estimate the system characteristics under contamination of physiological and measurement noises. The arterial barore ex system may be divided into the neural and peripheral arc subsystems. The neural arc represents the relationship between pressure inputs and efferent sympathetic nerve activity (SNA), which may be regarded as a controller subsystem. The peripheral arc represents the relationship between SNA and AP, which may be regarded as a plant subsystem. The neural arc reveals derivative characteristics whereas the peripheral arc reveals low-pass characteristics. Numerical simulations based on the analytical results indicate that the neural arc compensates for the slow peripheral arc to optimize the arterial barore ex system in achieving both stability and quickness. Impairment of arterial barore ex function is associated with cardiovascular diseases, and arti cial activation of the arterial barore ex system could be a device-based treatment for cardiovascular diseases associated with sympathetic hyperactivity. To improve the efcacy of such device-based therapy, we may need to understand the interactions between stimulated and non-stimulated barore ex systems. Although static sigmoidal nonlinearity of the arterial barore ex with threshold and saturation phenomena is well documented, dynamic nonlinearities are less understood. Further efforts are warranted to fully understand arterial barore ex function and to apply the knowledge to the medical eld.

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Implant- and anesthesia-related factors affecting cardiopulmonary threshold intensities for vagus nerve stimulation

et al. 2021

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Objective. Vagus nerve stimulation (VNS) is typically delivered at increasing stimulus intensity until a neurological or physiological response is observed (‘threshold’) for dose calibration, preclinically and therapeutically. Factors affecting VNS thresholds have not been studied systematically. In a rodent model of VNS we measured neural and physiological responses to increasing VNS intensity, determined neurological and physiological thresholds and examined the effect of implant- and anesthesia-related factors on thresholds. Approach. In acute and chronic vagus implants (45 and 20 rats, respectively) VNS was delivered under isoflurane, ketamine-xylazine, or awake conditions. Evoked compound action potentials (CAPs) were recorded and activation of different fiber types was extracted. Elicited physiological responses were registered, including changes in heart rate (HR), breathing rate (BR), and blood pressure (BP). CAP and physiological thresholds were determined. Main results. The threshold for evoking discernable CAPs (>10 µV) (CAP threshold) is significantly lower than what elicits 5%–10% drop in heart rate (heart rate threshold, HRT) (25 µA ± 1.8 vs. 80 µA ± 5.1, respectively; mean ± SEM). Changes in BP and small changes in BR (bradypnea) occur at lowest intensities (70 µA ± 8.3), followed by HR changes (80 µA ± 5.1) and finally significant changes in BR (apnea) (310 μA ± 32.5). HRT and electrode impedance are correlated in chronic (Pearson correlation r= 0.47; p< 0.001) but not in acute implants (r = −0.34; p NS); HRT and impedance both increase with implant age (r= 0.44; p< 0.001 and r = 0.64; p < 0.001, respectively). HRT is lowest when animals are awake (200 µA ± 35.5), followed by ketamine-xylazine (640 µA ± 151.5), and isoflurane (1000 µA ± 139.5). The sequence of physiological responses with increasing VNS intensity is the same in anesthetized and awake animals. Pulsing frequency affects physiological responses but not CAPs. Significance. Implant age, electrode impedance, and type of anesthesia affect VNS thresholds and should be accounted for when calibrating stimulation dose.

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Aortic depressor nerve stimulation does not impede the dynamic characteristics of the carotid sinus baroreflex in normotensive or spontaneously hypertensive rats

Cited by 4 publications

References 31 publications

Tonic aortic depressor nerve stimulation does not impede baroreflex dynamic characteristics concomitantly mediated by the stimulated nerve

Tonic aortic depressor nerve stimulation does not impede baroreflex dynamic characteristics concomitantly mediated by the stimulated nerve

Linear and Nonlinear Analysis of the Carotid Sinus Baroreflex Dynamic Characteristics

Implant- and anesthesia-related factors affecting cardiopulmonary threshold intensities for vagus nerve stimulation

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