Purinergic receptor stimulation induces calcium oscillations and smooth muscle contraction in small pulmonary veins
Author
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Henríquez, Mauricio
Author
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Fonseca, Marcelo
Author
dc.contributor.author
Pérez-Zoghbi, José
Admission date
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2018-11-16T12:51:29Z
Available date
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2018-11-16T12:51:29Z
Publication date
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2018-07
Cita de ítem
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Journal of Physiology, 596(13). Julio, 2018. 2491–2506 pp
es_ES
Identifier
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0022-3751
Identifier
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10.1113/JP274731
Identifier
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https://repositorio.uchile.cl/handle/2250/152652
Abstract
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The small pulmonary veins (SPVs) may play a role in the development of pulmonary hypertension and pulmonary oedema via active changes in SPV diameter, mediated by vascular smooth muscle cell (VSMC) contraction. However, the excitation-contraction coupling mechanisms during vasoconstrictor stimulation remain poorly understood in these veins. We used rat precision-cut lung slices and phase-contrast and confocal microscopy to investigate dynamic changes in SPV cross-sectional luminal area and intracellular Ca2+ signalling in their VSMCs. We found that the SPV (similar to 150 mu m in diameter) contract strongly in response to extracellular ATP and other vasoconstrictors, including angiotensin-II and endothelin-1. ATP-induced SPV contraction was fast, concentration-dependent, completely reversible upon ATP washout, and inhibited by purinergic receptor antagonists suramin and AR-C118925 but not by MRS2179. Immunofluorescence showed purinergic P2Y2 receptors expressed in SPV VSMCs. ATP-induced SPV contraction was inhibited by phospholipase C beta inhibitor U73122 and accompanied by intracellular Ca2+ oscillations in the VSMCs. These Ca2+ oscillations and SPV contraction were inhibited by the inositol 1,4,5-trisphosphate receptor inhibitor 2-APB but not by ryanodine. The results of the present study suggest that ATP-induced vasoconstriction in SPVs is associated with the activation of purinergic P2Y2 receptors in VSMCs and the generation of Ca2+ oscillations.
es_ES
Patrocinador
dc.description.sponsorship
This work was supported by grants from the American Heart Association (11SDG5670050) and the American Lung Association (RG-196192-N) to JFPZ and by grants from FONDECYT-Chile (1140468) and from University of Chile (ENL029/2017) to MH.