Chronic endothelin-1 blockade reduces sympathetic nerve activity in rabbits with heart failure

2001 ◽  
Vol 280 (6) ◽  
pp. R1906-R1913 ◽  
Author(s):  
J.-L. Liu ◽  
R. U. Pliquett ◽  
E. Brewer ◽  
K. G. Cornish ◽  
Y.-T. Shen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Receptor Antagonist ◽  
Sympathetic Nerve ◽  
Baroreflex Sensitivity ◽  
Sympathetic Nerve Activity ◽  
Arterial Baroreflex ◽  
Nerve Activity ◽  
Baroreflex Control ◽  
Endothelin 1 ◽  
Before And After

Endothelin-1 (ET-1) is elevated in chronic heart failure (CHF). In this study, we determined the effects of chronic ET-1 blockade on renal sympathetic nerve activity (RSNA) in conscious rabbits with pacing-induced CHF. Rabbits were chronically paced at 320–340 beats/min for 3–4 wk until clinical and hemodynamic signs of CHF were present. Resting RSNA and arterial baroreflex control of RSNA were determined. Responses were determined before and after the ET-1 antagonist L-754,142 (a combined ETA and ETB receptor antagonist, n = 5) was administered by osmotic minipump infusion (0.5 mg · kg−1 · h−1 for 48 h). In addition, five rabbits with CHF were treated with the specific ETA receptor antagonist BQ-123. Baseline RSNA (expressed as a percentage of the maximum nerve activity during sodium nitroprusside infusion) was significantly higher (58.3 ± 4.9 vs. 27.0 ± 1.0, P < 0.001), whereas baroreflex sensitivity was significantly lower in rabbits with CHF compared with control (3.09 ± 0.19 vs. 6.04 ± 0.73, P < 0.001). L-754,142 caused a time-dependent reduction in arterial pressure and RSNA in rabbits with CHF. In addition, BQ-123 caused a reduction in resting RSNA. For both compounds, RSNA returned to near control levels 24 h after removal of the minipump. These data suggest that ET-1 contributes to sympathoexcitation in the CHF state. Enhancement of arterial baroreflex sensitivity may further contribute to sympathoinhibition after ET-1 blockade in heart failure.

Role of endothelin-1 in mediating changes in cardiac sympathetic nerve activity in heart failure

2016 ◽  
Vol 310 (1) ◽  
pp. R94-R99 ◽  
Author(s):  
Yonis Abukar ◽  
Clive N. May ◽  
Rohit Ramchandra
Keyword(s):  
Heart Failure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Nerve Activity ◽  
Baroreflex Control ◽  
Endothelin 1 ◽  
Significant Impairment ◽  
Severity Of The Disease ◽  
Spontaneous Baroreflex

Heart failure (HF) is associated with increased sympathetic nerve activity to the heart (CSNA), which is directly linked to mortality in HF patients. Previous studies indicate that HF is associated with high levels of plasma endothelin-1 (ET-1), which correlates with the severity of the disease. We hypothesized that blockade of endothelin receptors would decrease CSNA. The effects of intravenous tezosentan (a nonselective ETA and ETB receptor antagonist) (8 mg·kg−1·h−1) on resting levels of CSNA, arterial pressure, and heart rate were determined in conscious normal sheep ( n = 6) and sheep with pacing-induced HF ( n = 7). HF was associated with a significant decrease in ejection fraction (from 74 ± 2% to 38 ± 1%, P < 0.001) and a significant increase in resting levels of CSNA burst incidence (from 56 ± 11 to 87 ± 2 bursts/100 heartbeats, P < 0.01). Infusion of tezosentan for 60 min significantly decreased resting mean aterial pressure (MAP) in both normal and HF sheep (−8 ± 4 mmHg and −4 ± 3 mmHg, respectively; P < 0.05). This was associated with a significant decrease in CSNA (by 25 ± 26% of control) in normal sheep, but there was no change in CSNA in HF sheep. Calculation of spontaneous baroreflex gain indicated significant impairment of the baroreflex control of HR after intravenous tezosentan infusion in normal animals but no change in HF animals. These data suggest that endogenous levels of ET-1 contribute to the baseline levels of CSNA in normal animals, but this effect is absent in HF.

scholarly journals Exercise training prevents the deterioration in the arterial baroreflex control of sympathetic nerve activity in chronic heart failure patients

2015 ◽  
Vol 308 (9) ◽  
pp. H1096-H1102 ◽  
Author(s):  
Raphaela V. Groehs ◽  
Edgar Toschi-Dias ◽  
Ligia M. Antunes-Correa ◽  
Patrícia F. Trevizan ◽  
Maria Urbana P. B. Rondon ◽  
...  
Keyword(s):  
Heart Failure ◽  
Time Delay ◽  
Exercise Training ◽  
Arterial Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Arterial Baroreflex ◽  
Nerve Activity ◽  
Baroreflex Control

Arterial baroreflex control of muscle sympathetic nerve activity (ABRMSNA) is impaired in chronic systolic heart failure (CHF). The purpose of the study was to test the hypothesis that exercise training would improve the gain and reduce the time delay of ABRMSNA in CHF patients. Twenty-six CHF patients, New York Heart Association Functional Class II-III, EF ≤ 40%, peak V̇o2 ≤ 20 ml·kg−1·min−1 were divided into two groups: untrained (UT, n = 13, 57 ± 3 years) and exercise trained (ET, n = 13, 49 ± 3 years). Muscle sympathetic nerve activity (MSNA) was directly recorded by microneurography technique. Arterial pressure was measured on a beat-to-beat basis. Time series of MSNA and systolic arterial pressure were analyzed by autoregressive spectral analysis. The gain and time delay of ABRMSNA was obtained by bivariate autoregressive analysis. Exercise training was performed on a cycle ergometer at moderate intensity, three 60-min sessions per week for 16 wk. Baseline MSNA, gain and time delay of ABRMSNA, and low frequency of MSNA (LFMSNA) to high-frequency ratio (HFMSNA) (LFMSNA/HFMSNA) were similar between groups. ET significantly decreased MSNA. MSNA was unchanged in the UT patients. The gain and time delay of ABRMSNA were unchanged in the ET patients. In contrast, the gain of ABRMSNA was significantly reduced [3.5 ± 0.7 vs. 1.8 ± 0.2, arbitrary units (au)/mmHg, P = 0.04] and the time delay of ABRMSNA was significantly increased (4.6 ± 0.8 vs. 7.9 ± 1.0 s, P = 0.05) in the UT patients. LFMSNA-to-HFMSNA ratio tended to be lower in the ET patients ( P < 0.08). Exercise training prevents the deterioration of ABRMSNA in CHF patients.

Hyperventilation alters arterial baroreflex control of heart rate and muscle sympathetic nerve activity

2000 ◽  
Vol 279 (2) ◽  
pp. H536-H541 ◽  
Author(s):  
Philippe Van de Borne ◽  
Silvia Mezzetti ◽  
Nicola Montano ◽  
Krzysztof Narkiewicz ◽  
Jean Paul Degaute ◽  
...  
Keyword(s):  
Heart Rate ◽  
Sympathetic Nerve ◽  
Baroreflex Sensitivity ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Normal Subjects ◽  
Arterial Baroreflex ◽  
Baroreceptor Sensitivity ◽  
Nerve Activity ◽  
Baroreflex Control

Interactions between mechanisms governing ventilation and blood pressure (BP) are not well understood. We studied in 11 resting normal subjects the effects of sustained isocapnic hyperventilation on arterial baroreceptor sensitivity, determined as the α index between oscillations in systolic BP (SBP) generated by respiration and oscillations present in R-R intervals (RR) and in peripheral sympathetic nerve traffic [muscle sympathetic nerve activity (MSNA)]. Tidal volume increased from 478 ± 24 to 1,499 ± 84 ml and raised SBP from 118 ± 2 to 125 ± 3 mmHg, whereas RR decreased from 947 ± 18 to 855 ± 11 ms (all P < 0.0001); MSNA did not change. Hyperventilation reduced arterial baroreflex sensitivity to oscillations in SBP at both cardiac (from 13 ± 1 to 9 ± 1 ms/mmHg, P < 0.001) and MSNA levels (by −37 ± 5%, P < 0.0001). Thus increased BP during hyperventilation does not elicit any reduction in either heart rate or MSNA. Baroreflex modulation of RR and MSNA in response to hyperventilation-induced BP oscillations is attenuated. Blunted baroreflex gain during hyperventilation may be a mechanism that facilitates simultaneous increases in BP, heart rate, and sympathetic activity during dynamic exercise and chemoreceptor activation.

alpha-ANP alters reflex control of lumbar and renal sympathetic nerve activity and heart rate

1987 ◽  
Vol 253 (5) ◽  
pp. H1136-H1140 ◽  
Author(s):  
T. Imaizumi ◽  
A. Takeshita ◽  
H. Higashi ◽  
M. Nakamura
Keyword(s):  
Heart Rate ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Vagal Afferents ◽  
Arterial Baroreflex ◽  
Nerve Activity ◽  
Baroreflex Control ◽  
Arterial Baroreceptors ◽  
Before And After ◽  
Bilateral Vagotomy

This study examined the effects of synthetic alpha-rat atrial natriuretic peptide (alpha-rANP) on arterial pressure (AP), heart rate (HR), and renal and lumbar sympathetic nerve activity (SNA) in rats with intact arterial baroreceptors before and after bilateral vagotomy and in those with sinoaortic denervation before and after vagotomy. In intact rats, alpha-rANP decreased AP, which was accompanied by the decrease in renal SNA ad HR and no change in lumbar SNA. In contrast, the increase in lumbar SNA and HR occurred during hypotension caused by nitroglycerin. In rats with intact arterial baroreceptors and vagi sectioned, renal and lumbar SNA and HR did not change during hypotension with alpha-rANP. In addition, alpha-rANP did not alter the gain of arterial baroreflex control of lumbar SNA in these rats. In rats with sinoaortic denervation, alpha-rANP decreased HR and renal and lumbar SNA before vagotomy but did not change them after vagotomy. These results suggest, first, that alpha-rANP activates vagal afferents and thereby inhibits renal and lumbar SNA and HR and, second, that alpha-rANP may reset arterial baroreflex control of SNA and HR to a lower pressure range.

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