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.

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.

scholarly journals Activation of NTS A2a adenosine receptors differentially resets baroreflex control of renal vs. adrenal sympathetic nerve activity

2009 ◽  
Vol 296 (4) ◽  
pp. H1058-H1068 ◽  
Author(s):  
Tomoko K. Ichinose ◽  
Donal S. O'Leary ◽  
Tadeusz J. Scislo
Keyword(s):  
Receptor Antagonist ◽  
Adenosine Receptors ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Response Curves ◽  
Nerve Activity ◽  
Baroreflex Control ◽  
A2a Adenosine Receptors ◽  
Stimulation Of

The role of nucleus of solitary tract (NTS) A2a adenosine receptors in baroreflex mechanisms is controversial. Stimulation of these receptors releases glutamate within the NTS and elicits baroreflex-like decreases in mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA), whereas inhibition of these receptors attenuates HR baroreflex responses. In contrast, stimulation of NTS A2a adenosine receptors increases preganglionic adrenal sympathetic nerve activity (pre-ASNA), and the depressor and sympathoinhibitory responses are not markedly affected by sinoaortic denervation and blockade of NTS glutamatergic transmission. To elucidate the role of NTS A2a adenosine receptors in baroreflex function, we compared full baroreflex stimulus-response curves for HR, RSNA, and pre-ASNA (intravenous nitroprusside/phenylephrine) before and after bilateral NTS microinjections of selective adenosine A2a receptor agonist (CGS-21680; 2.0, 20 pmol/50 nl), selective A2a receptor antagonist (ZM-241385; 40 pmol/100 nl), and nonselective A1 + A2a receptor antagonist (8-SPT; 1 nmol/100 nl) in urethane/α-chloralose anesthetized rats. Activation of A2a receptors decreased the range, upper plateau, and gain of baroreflex-response curves for RSNA, whereas these parameters all increased for pre-ASNA, consistent with direct effects of the agonist on regional sympathetic activity. However, no resetting of baroreflex-response curves along the MAP axis occurred despite the marked decreases in baseline MAP. The antagonists had no marked effects on baseline variables or baroreflex-response functions. We conclude that the activation of NTS A2a adenosine receptors differentially alters baroreflex control of HR, RSNA, and pre-ASNA mostly via non-baroreflex mechanism(s), and these receptors have virtually no tonic action on baroreflex control of these sympathetic outputs.

scholarly journals Baroreflex control of renal sympathetic nerve activity in early heart failure assessed by the sequence method

2017 ◽  
Vol 595 (11) ◽  
pp. 3319-3330 ◽  
Author(s):  
Renata Maria Lataro ◽  
Luiz Eduardo Virgilio Silva ◽  
Carlos Alberto Aguiar Silva ◽  
Helio Cesar Salgado ◽  
Rubens Fazan
Keyword(s):  
Heart Failure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Nerve Activity ◽  
Baroreflex Control ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic Nerve ◽  
Sequence Method ◽  
Renal Sympathetic

Role of prostaglandins in determining the increased cardiac sympathetic nerve activity in ovine sepsis

2014 ◽  
Vol 307 (1) ◽  
pp. R75-R81 ◽  
Author(s):  
Lindsea C. Booth ◽  
Rohit Ramchandra ◽  
Paolo Calzavacca ◽  
Clive N. May
Keyword(s):  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Prostaglandin E ◽  
Nerve Activity ◽  
Baroreflex Control ◽  
E Coli ◽  
Inhibition Of Prostaglandin Synthesis ◽  
Conscious Sheep ◽  
Hyperdynamic Sepsis

Effective treatment of sepsis remains a significant challenge in intensive care units. During sepsis, there is widespread activation of the sympathetic nervous system, which is thought to have both beneficial and detrimental effects. The sympathoexcitation is thought to be partly due to the developing hypotension, but may also be a response to the inflammatory mediators released. Thus, we investigated whether intracarotid infusion of prostaglandin E2 (PGE2) induced similar cardiovascular changes to those caused by intravenous infusion of Escherichia coli in sheep and whether inhibition of prostaglandin synthesis, with the nonselective cyclooxygenase inhibitor indomethacin, administered at 2 and 8 h after the onset of sepsis, reduced sympathetic nerve activity (SNA), and heart rate (HR). Studies were performed in conscious sheep instrumented to measure mean arterial pressure (MAP), HR, cardiac SNA (CSNA), and renal SNA (RSNA). Intracarotid infusion of PGE2 (50 ng·kg−1·min−1) increased temperature, CSNA, and HR, but not MAP or RSNA. Sepsis, induced by infusion of E. coli, increased CSNA, but caused an initial, transient inhibition of RSNA. At 2 h of sepsis, indomethacin (1.25 mg/kg bolus) increased MAP and caused reflex decreases in HR and CSNA. After 8 h of sepsis, indomethacin did not alter MAP, but reduced CSNA and HR, without altering baroreflex control. These findings indicate an important role for prostaglandins in mediating the increase in CSNA and HR during the development of hyperdynamic sepsis, whereas prostaglandins do not have a major role in determining the early changes in RSNA.

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.

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