Endothelin-1 contributes to increased NFATc3 activation by chronic hypoxia in pulmonary arteries

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Endothelin-1 contributes to increased NFATc3 activation by chronic hypoxia in pulmonary arteries.

Chronic hypoxia (CH) activates the Ca(2+)-dependent transcription factor nuclear factor of activated T cells isoform c3 (NFATc3) in mouse pulmonary arteries. However, the mechanism of this response has not been explored. Since we have demonstrated that NFATc3 is required for CH-induced pulmonary arterial remodeling, establishing how CH activates NFATc3 is physiologically significant. The goal o...

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NFATc3 contributes to intermittent hypoxia-induced arterial remodeling in mice.

Sleep apnea (SA) is defined as intermittent respiratory arrest during sleep and affects up to 20% of the adult population. SA is also associated with an increased incidence of hypertension and peripheral vascular disease. Exposing rodents to intermittent hypoxia during sleep mimics the cyclical hypoxia/normoxia of SA. We have previously shown that in mice and rats intermittent hypoxia induces E...

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Increased endothelial exocytosis and generation of endothelin-1 contributes to constriction of aged arteries.

RATIONALE Circulating levels of endothelin (ET)-1 and endogenous ET(A)-mediated constriction are increased in human aging. The mechanisms responsible are not known. OBJECTIVE Investigate the storage, release, and activity of ET-1 system in arteries from young and aged Fischer-344 rats. METHODS AND RESULTS After NO synthase inhibition (L-NAME), thrombin contracted aged arteries, which was in...

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Activation of hypoxia-inducible factor-1 in pulmonary arterial smooth muscle cells by endothelin-1.

Numerous cellular responses to hypoxia are mediated by the transcription factor hypoxia-inducible factor-1 (HIF-1). HIF-1 plays a central role in the pathogenesis of hypoxic pulmonary hypertension. Under certain conditions, HIF-1 may utilize feedforward mechanisms to amplify its activity. Since hypoxia increases endothelin-1 (ET-1) levels in the lung, we hypothesized that during moderate, prolo...

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Pulmonary artery smooth muscle cell endothelin-1 expression modulates the pulmonary vascular response to chronic hypoxia.

Endothelin-1 (ET-1) increases pulmonary vascular tone through direct effects on pulmonary artery smooth muscle cells (PASMC) via membrane-bound ET-1 receptors. Circulating ET-1 contributes to vascular remodeling by promoting SMC proliferation and migration and inhibiting SMC apoptosis. Although endothelial cells (EC) are the primary source of ET-1, whether ET-1 produced by SMC modulates pulmona...

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ژورنال

عنوان ژورنال: American Journal of Physiology-Cell Physiology

سال: 2011

ISSN: 0363-6143,1522-1563

DOI: 10.1152/ajpcell.00029.2011