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Purinergic regulation of pulmonary vascular tone

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Abstract

Purinergic signaling is a crucial determinant in the regulation of pulmonary vascular physiology and presents a promising avenue for addressing lung diseases. This intricate signaling system encompasses two primary receptor classes: P1 and P2 receptors. P1 receptors selectively bind adenosine, while P2 receptors exhibit an affinity for ATP, ADP, UTP, and UDP. Functionally, P1 receptors are associated with vasodilation, while P2 receptors mediate vasoconstriction, particularly in basally relaxed vessels, through modulation of intracellular Ca2+ levels. The P2X subtype receptors facilitate extracellular Ca2+ influx, while the P2Y subtype receptors are linked to endoplasmic reticulum Ca2+ release. Notably, the primary receptor responsible for ATP-induced vasoconstriction is P2X1, with α,β-meATP and UDP being identified as potent vasoconstrictor agonists. Interestingly, ATP has been shown to induce endothelium-dependent vasodilation in pre-constricted vessels, associated with nitric oxide (NO) release. In the context of P1 receptors, adenosine stimulation of pulmonary vessels has been unequivocally demonstrated to induce vasodilation, with a clear dependency on the A2B receptor, as evidenced in studies involving guinea pigs and rats. Importantly, evidence strongly suggests that this vasodilation occurs independently of endothelium-mediated mechanisms. Furthermore, studies have revealed variations in the expression of purinergic receptors across different vessel sizes, with reports indicating notably higher expression of P2Y1, P2Y2, and P2Y4 receptors in small pulmonary arteries. While the existing evidence in this area is still emerging, it underscores the urgent need for a comprehensive examination of the specific characteristics of purinergic signaling in the regulation of pulmonary vascular tone, particularly focusing on the disparities observed across different intrapulmonary vessel sizes. Consequently, this review aims to meticulously explore the current evidence regarding the role of purinergic signaling in pulmonary vascular tone regulation, with a specific emphasis on the variations observed in intrapulmonary vessel sizes. This endeavor is critical, as purinergic signaling holds substantial promise in the modulation of vascular tone and in the proactive prevention and treatment of pulmonary vascular diseases.

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Acknowledgements

We thank Santiago Ramirez (UTHealth | The University of Texas Health Science Center at Houston) for English correction of the manuscript.

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Authors and Affiliations

  1. Programa de Fisiología y Biofísica, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina Universidad de Chile, Independencia 1027, 7500975, Independencia, Santiago, Chile

    Marco Alveal, Andrea Méndez, Aline García & Mauricio Henríquez

  2. Escuela de Kinesiología, Facultad de Salud y Ciencias Sociales, Campus Providencia, Sede Santiago, Universidad de Las Américas, Santiago, Chile

    Andrea Méndez

  3. Escuela de Graduados, Facultad de Ciencias Veterinarias,, Universidad Austral de Chile, Valdivia, Chile

    Aline García

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  1. Marco Alveal
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  2. Andrea Méndez
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  3. Aline García
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  4. Mauricio Henríquez
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MA made substantial contributions to the conception and design of the work and data interpretation; drafted, revised, and approved the submitted version; and has agreed to be accountable.

AM made substantial contributions to the review design and data interpretation, revised and approved the submitted version of the manuscript, and has agreed to be accountable.

AG has drafted and revised the manuscript, approved the submitted version, and has agreed to be accountable.

MH made substantial contributions to the conception and design of the work and data interpretation; drafted, revised, and approved the submitted version; and has agreed to be accountable.

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Correspondence to Mauricio Henríquez.

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Alveal, M., Méndez, A., García, A. et al. Purinergic regulation of pulmonary vascular tone. Purinergic Signalling (2024). https://doi.org/10.1007/s11302-024-10010-5

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