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The pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of prostacyclin and EDRF

William Harvey Research Institute, St Bartholomew's Hospital Medical College, London, United Kingdom.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 01/1989; 85(24):9797-800. DOI: 10.1073/pnas.85.24.9797
Source: PubMed

ABSTRACT Endothelin releases prostacyclin and thromboxane A2 from guinea pig or rat isolated lungs and endothelium-derived relaxing factor in the perfused mesentery of the rat. Endothelin is also substantially removed by the pulmonary circulation of the rat in vitro and in vivo and by guinea pig lungs in vitro. In the rat, the effects of endothelin on the blood pressure vary from pressor (in pithed rats) to purely depressor in anesthetized rats where the resting blood pressure is high. It therefore has the characteristics of a local pressor hormone, rather than a circulating one.

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    • "In order to exclude any effects of nitric oxide (NO), which modulate both the production and the action of ET-1 (de Nucci et al., 1988; Boulanger and Lüscher, 1990; Vanhoutte, 2000; Félétou et al., 2012) and the release of which could be initiated by ET-1 or serotonin acting on ET B or 5-HT 1D receptors, respectively (Cohen et al., 1983; de Nucci et al., 1988; Schoeffter and Hoyer, 1990; Schini et al., 1991; Hirata et al., 1993), all experiments were performed in the presence of a NO synthase inhibitor. The rings were equilibrated for at least ten minutes prior to incubation with the non-selective nitric oxide synthase inhibitor N ω -nitro-L-arginine methyl ester (L-NAME, 3 × 10 −4 mol/L) for 30 min to block basal and receptor-stimulated generation of NO (Widmer et al., 2006; Baretella et al., 2013). "
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    • "Within blood vessels, both receptors are found on smooth muscle cells and their activation results in vasoconstriction. ETB receptors are, however, predominantly found on the vascular endothelium where their activation results in vasodilatation via prostacyclin and NO (DeNucci et al., 1988). Because most ET-1 is released abluminally, plasma concentrations of ET-1 do not accurately reflect ET-1 production. "
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    • "In principal cells of the collecting duct, activation of ET B receptors inhibits sodium and water transport [16]. ET B receptors also mediate clearance of endothelin from the circulation [17], and this effect appears to involve cross-talk with the ET A receptor, at least under physiological conditions [18]. In the vasculature and the kidney, via activation of its ET A receptors, endothelin has a basal ( " tonic " ) vasoconstricting role; endothelins also contribute to myocardial Biochimica et Biophysica Acta 1802 (2010) 1203–1213 "
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