Endothelin in Human Brain and Pituitary Gland

Takahashi, Kazuhiro; Ghatei, M. A.; Jones, P. M.; Murphy, J. K.; Lam, Hing‐Chung; O'Halloran, D.J.; Bloom, Stephen R.

doi:10.1097/00005344-199100177-00026

Cited by 30 publications

(14 citation statements)

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“…These results suggest that baseline endogenous levels of ET-1 tonically stimulates the baseline level of CSNA in normal animals. In terms of the site of action of ET-1, previous studies have reported the presence of ET-1 receptors in many brain regions, including regions that are considered important in the regulation of the cardiovascular system such as the area postrema, SFO and paraventricular nucleus (1,11,12,25,36). Importantly, the area postrema and SFO are circumventricular organs and can be accessed by ET-1 and tezosentan, which do not cross the blood-brain barrier.…”

Section: Discussionmentioning

confidence: 99%

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

Abukar

May

Ramchandra

2016

American Journal of Physiology-Regulatory, Integrative and Comp

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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.

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Section: Discussionmentioning

confidence: 99%

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

Abukar

May

Ramchandra

2016

American Journal of Physiology-Regulatory, Integrative and Comp

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“…ECE-1 has been mapped to these same areas (522, 816). ET-3 mRNA and peptide are found in more rostral brain regions (469, 748, 749). ET-1 protein and mRNA are also abundant in choroid plexus (521) from which ET-1 may easily enter the cerebrospinal fluid (CSF).…”

Section: Endothelin and The Nervous Systemmentioning

confidence: 99%

Regulation of Blood Pressure and Salt Homeostasis by Endothelin

Kohan

Rossi

Inscho

et al. 2011

Physiological Reviews

373

459

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Endothelin (ET) peptides and their receptors are intimately involved in the physiological control of systemic blood pressure and body Na homeostasis, exerting these effects through alterations in a host of circulating and local factors. Hormonal systems affected by ET include natriuretic peptides, aldosterone, catecholamines, and angiotensin. ET also directly regulates cardiac output, central and peripheral nervous system activity, renal Na and water excretion, systemic vascular resistance, and venous capacitance. ET regulation of these systems is often complex, sometimes involving opposing actions depending on which receptor isoform is activated, which cells are affected, and what other prevailing factors exist. A detailed understanding of this system is important; disordered regulation of the ET system is strongly associated with hypertension and dysregulated extracellular fluid volume homeostasis. In addition, ET receptor antagonists are being increasingly used for the treatment of a variety of diseases; while demonstrating benefit, these agents also have adverse effects on fluid retention that may substantially limit their clinical utility. This review provides a detailed analysis of how the ET system is involved in the control of blood pressure and Na homeostasis, focusing primarily on physiological regulation with some discussion of the role of the ET system in hypertension.

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“…ET-1 mRNA has been localised in porcine spinal cord (Giaid et al, 1989), the rat cerebellum (MacCumber et al, 1989;MacCumber et al, 1990) and the posterior pituitary system of rat and swine (Yoshizawa et al, 1990). In the rat brain, immunoreactive ET-1 has been localised in 17 regions (Matsumoto et al, 1989;Yoshizawa et al, 1989;Yoshizawa et al, 1990;Takahashi et al, 1991a;Takahashi et al, 1991b). ECE-1 has been detected in the rat hypothalamus, midbrain, cerebral cortex, cerebellum, medulla oblongata, olfactory bulb, striatum, hippocampus (Warner et al, 1992a) and astrocytes (Barnes et al, 1997).…”

Section: Introductionmentioning

confidence: 99%