Effects of neuronal norepinephrine uptake blockade on baroreflex neural and peripheral arc transfer characteristics

Kawada, Toru; Miyamoto, Tadayoshi; Uemura, Kazunori; Kashihara, Koji; Kamiya, Atsunori; Sugimachi, Masaru; Sunagawa, Kenji

doi:10.1152/ajpregu.00527.2003

Cited by 13 publications

(20 citation statements)

References 32 publications

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“…Despite the significant alteration in the sympathetic HR control, the total baroreflex transfer function did not differ between WKY and SHR, suggesting little contribution of HR to the determination of dynamic AP regulation. The lack of significant effect of HR on the dynamic AP regulation is consistent with the findings in rabbits (13,25).…”

Section: Discussionsupporting

confidence: 91%

“…endings is norepinephrine. The peripheral arc transfer function may thus reflect the combined dynamic properties of norepinephrine kinetics at the neuroeffector junction and the effector response to adrenergic stimulation (13). Neuronal uptake and ␣-adrenergic autoinhibition of norepinephrine operate to the same extent during electrical stimulation of the spinal cord in both SHR and WKY (36).…”

Section: Discussionmentioning

confidence: 99%

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Dynamic characteristics of baroreflex neural and peripheral arcs are preserved in spontaneously hypertensive rats

Kawada

Shimizu

Kamiya

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Although baroreceptors are known to reset to operate in a higher pressure range in spontaneously hypertensive rats (SHR), the total profile of dynamic arterial pressure (AP) regulation remains to be clarified. We estimated open-loop transfer functions of the carotid sinus baroreflex in SHR and Wistar Kyoto (WKY) rats. Mean input pressures were set at 120 (WKY120 and SHR120) and 160 mmHg (SHR160). The neural arc transfer function from carotid sinus pressure to efferent splanchnic sympathetic nerve activity (SNA) revealed derivative characteristics in both WKY and SHR. The slope of dynamic gain (in decibels per decade) between 0.1 and 1 Hz was not different between WKY120 (10.1 ± 1.0) and SHR120 (10.4 ± 1.1) but was significantly greater in SHR160 (13.2 ± 0.8, P < 0.05 with Bonferroni correction) than in SHR120. The peripheral arc transfer function from SNA to AP showed low-pass characteristics. The slope of dynamic gain (in decibels per decade) did not differ between WKY120 (−34.0 ± 1.2) and SHR120 (−31.4 ± 1.0) or between SHR120 and SHR160 (−32.8 ± 1.3). The total baroreflex showed low-pass characteristics and the dynamic gain at 0.01 Hz did not differ between WKY120 (0.91 ± 0.08) and SHR120 (0.84 ± 0.13) or between SHR120 and SHR160 (0.83 ± 0.11). In both WKY and SHR, the declining slope of dynamic gain was significantly gentler for the total baroreflex than for the peripheral arc, suggesting improved dynamic AP response in the total baroreflex. In conclusion, the dynamic characteristics of AP regulation by the carotid sinus baroreflex were well preserved in SHR despite significantly higher mean AP.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Dynamic characteristics of baroreflex neural and peripheral arcs are preserved in spontaneously hypertensive rats

Kawada

Shimizu

Kamiya

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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“…The peripheral arc acted like a low-pass filter such that the transfer of fast changes in nerve activity (Ͼ0.1 Hz) to the vasculature is damped. 27,28 We found almost identical transfer functions with placebo and with yohimbine. In healthy young subjects, endogenous ␣-2 adrenergic tone may not be sufficient to alter the shape of the sympathetic baroreflex curve or the filter characteristics of the sympathetic baroreflex.…”

Section: Tank Et Al Yohimbine and Heart Rate 901supporting

confidence: 51%

Yohimbine Attenuates Baroreflex-Mediated Bradycardia in Humans

et al. 2007

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Abstract-␣-2 Adrenoreceptor stimulation profoundly augments baroreflex-mediated bradycardia presumably through parasympathetic activation. We tested the hypothesis that endogenous ␣-2 adrenergic tone mediates a similar response. In 10 healthy men (age: 33Ϯ3 years; body mass index: 24Ϯ1.3 kg/m 2 ), we determined baroreflex control of heart rate and sympathetic traffic after ingestion of the selective ␣-2 adrenoceptor antagonist yohimbine (20 mg) or placebo. Testing was conducted in a randomized, double-blind, crossover fashion. We measured heart rate, brachial and finger blood pressure, and muscle sympathetic nerve activity. Sympathetic and parasympathetic baroreflex curves were determined using incremental phenylephrine and nitroprusside infusions (0.3, 0.6, 0.9, 1.2, and 1.5 g/kg per minute). Plasma norepinephrine increased with yohimbine (50Ϯ38 ng/L; PϽ0.05) and was unchanged with placebo (2.2Ϯ7.6 ng/L). Blood pressure increased 13Ϯ4/8Ϯ1 mm Hg with yohimbine and 6Ϯ2/3Ϯ1 mm Hg with placebo (PϽ0.01). HR increased 5Ϯ1 bpm with yohimbine but did not change with placebo (PϽ0.01). Ninety minutes after drug ingestion, resting muscle sympathetic nerve activity was similar with yohimbine and with placebo. Baroreflex control of heart rate was decreased with yohimbine (6 ms/mm Hg versus 10 ms/mm Hg; PϽ0.01) and reset to higher blood pressure and heart rate values. In contrast, yohimbine did not alter the sympathetic baroreflex curve. Yohimbine selectively attenuates baroreflex heart rate control in normotensive young men possibly through parasympathetic mechanisms.

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“…Although the SNS we used is different from a physiological discharge of nerve fibers, the HR response to physiological nerve discharge would obey the same principle characterized by the transfer function from SNS to HR. When we estimated the transfer function from recorded sympathetic nerve activity to HR, it also approximates to the second-order low-pass filter with pure dead time [25].…”

Section: Appendix Amentioning

confidence: 99%

Sympathetic Neural Regulation of Heart Rate Is Robust against High Plasma Catecholamines

Kawada

Miyamoto²,

Miyoshi³

et al. 2006

J. Physiol. Sci

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Abstract:The sympathetic regulation of heart rate (HR) may be attained by neural and humoral factors. With respect to the humoral factor, plasma noradrenaline (NA) and adrenaline (Adr) can reportedly increase to levels approximately 10 times higher than resting level during severe exercise. Whether such high plasma NA or Adr interfered with the sympathetic neural regulation of HR remained unknown. We estimated the transfer function from cardiac sympathetic nerve stimulation (SNS) to HR in anesthetized and vagotomized rabbits. An intravenous administration of NA (n = 6) at 1 and 10 µg·kg -1 ·h -1 increased plasma NA concentration (pg/ml) from a baseline level of 438 ± 117 (mean ± SE) to 974 ± 106 and 6,830 ± 917 (P < 0.01), respectively. The dynamic gain (bpm/Hz) of the transfer function did not change significantly (from 7.6 ± 1.2 to 7.5 ± 1.1 and 8.1 ± 1.1), whereas mean HR (in bpm) during SNS slightly increased from 280 ± 24 to 289 ± 22 (P < 0.01) and 288 ± 22 (P < 0.01). The intravenous administration of Adr (n = 6) at 1 and 10 µg·kg -1 ·h -1 increased plasma Adr concentration (pg/ml) from a baseline level of 257 ± 86 to 659 ± 172 and 2,760 ± 590 (P < 0.01), respectively. Neither the dynamic gain (from 8.0 ± 0.6 to 8.4 ± 0.8 and 8.2 ± 1.0) nor the mean HR during SNS (from 274 ± 13 to 275 ± 13 and 274 ± 13) changed significantly. In contrast, the intravenous administration of isoproterenol (n = 6) at 10 µg·kg -1 ·h -1 significantly increased mean HR during SNS (from 278 ± 11 to 293 ± 9, P < 0.01) and blunted the transfer gain value at 0.0078 Hz (from 5.9 ± 1.0 to 1.0 ± 0.4, P < 0.01). In conclusion, high plasma NA or Adr hardly affected the dynamic sympathetic neural regulation of HR.Key words: systems analysis, neuro-humoral interaction, noradrenaline, adrenaline, isoproterenol.The sympathetic regulation of heart rate (HR) may be attained by neural and humoral factors. One unique feature of the neural regulation, which is in contrast to the humoral regulation, is its quickness. The quickness of regulation may be best quantified by identifying dynamic characteristics of the input-output or stimulus-response relationship of a given system [1, 2]. Although we have identified the dynamic characteristics of the HR regulation by the cardiac sympathetic nerve by using a transfer function analysis [3, 4], we ignored the possible effects of plasma catecholamines on the transfer function. Plasma concentrations of noradrenaline (NA) and adrenaline (Adr) can increase during systemic sympathetic activation. For instance, plasma NA and Adr both increase to approximately 10 times their respective resting levels during severe exercise [5]. They increase to approximately 6 and 20 times, respectively, during acute myocardial infarction [5]. Whether such high plasma NA or Adr interfered with the dynamic sympathetic neural regulation of HR remained unanswered.Two mutually opposing hypotheses can be put forward regarding interactions between the humoral and neural factors in the sympathetic regulation of HR. The activation of pre...

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Effects of neuronal norepinephrine uptake blockade on baroreflex neural and peripheral arc transfer characteristics

Cited by 13 publications

References 32 publications

Dynamic characteristics of baroreflex neural and peripheral arcs are preserved in spontaneously hypertensive rats

Dynamic characteristics of baroreflex neural and peripheral arcs are preserved in spontaneously hypertensive rats

Yohimbine Attenuates Baroreflex-Mediated Bradycardia in Humans

Sympathetic Neural Regulation of Heart Rate Is Robust against High Plasma Catecholamines

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