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

Abstract

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.

Activation of neuronal endothelin B receptors mediates pressor response through alpha-1 adrenergic receptors

“…; Abukar et al. ). In a series of experiments using anesthetized dogs, Morimoto's group described an inhibitory effect of intrarenal infusions of S6c on renal nerve stimulation‐induced antidiuresis and norepinephrine overflow suggesting an inhibitory role for ET B receptors on efferent sympathetic nerve terminal release of norepinephrine (Matsumura et al.…”

Prognostic performance of serial in‐hospital measurements of copeptin and multiple novel biomarkers among patients with worsening heart failure: results from the MOLITOR study

“…Endothelin‐1 is a vasoconstrictor peptide, which is produced by vascular tissue, and increases blood pressure. HF patients are often found with elevated levels of ET‐1, as a result of neurohormonal activation 12. Due to its instability, the C‐terminal portion of pro‐endothelin‐1, which is much more stable, is commonly being measured.…”

“…HF patients are often found with elevated levels of ET-1, as a result of neurohormonal activation. 12 Due to its instability, the C-terminal portion of pro-endothelin-1, which is much more stable, is commonly being measured. Atrial natriuretic peptide (ANP) is released from the atria as a response to elevated intra-atrial pressure and wall stretch, 13 but its concentrations are difficult to be measured due to its short half-life (2-5 min).…”

Endothelin-1-Mediated Mechanisms in the Carotid Body Modulates Cardiovascular Responses in Rats Exposed to Chronic Intermittent Hypoxia

“…ET-1 is a vasoactive peptide and is mainly expressed in the endothelium, blood vessels and CB glomus cells exposed to CIH (Atanasova and Lazarov 2016). The level of ET-1 is important in the maintenance of normal cardiovascular function, as its imbalance leads to systemic hypertension, arrhythmia and heart failure (Abukar et al 2016;Lehmann et al 2014a, b;Palma et al 2002). In particular, ET-1, in the CB glomus cells, is known to play an important role in peripheral chemoreceptor activation after CIH exposure (Iturriaga et al 2015).…”