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. 2025 Apr 16.
doi: 10.1007/s11302-025-10086-7. Online ahead of print.

Involvement of purinergic signalling in the vasomotor response to hypochlorous acid in porcine coronary artery

Ashwaq Baghdadi  1 , William R Dunn  1 , Vera Ralevic  2
Affiliations

Involvement of purinergic signalling in the vasomotor response to hypochlorous acid in porcine coronary artery

Ashwaq Baghdadi et al. Purinergic Signal. .

Abstract

Hypochlorous acid (HOCl) is generated by neutrophils during the innate immune response. ATP is released from cells by various stimuli and during inflammation but whether ATP is released by and participates in the response to HOCl is unclear. This study investigated vasomotor effects of HOCl on the porcine coronary artery (PCA) and the involvement of ATP and purine receptors. HOCl at 100 μM induced rapid and transient endothelium-dependent relaxation followed by slow and sustained endothelium-independent relaxation. Transient endothelium-dependent relaxation was induced by 500 μM HOCl, followed by endothelium-dependent contraction, then slow endothelium-independent relaxation. 8-(p-sulphophenyl)theophylline (8-SPT), an adenosine/P1 receptor antagonist, blocked rapid relaxation and contraction to HOCl but an A2A receptor antagonist, ZM 241385, and an A1 receptor antagonist, DPCPX, had no effect. Suramin, a P2 receptor antagonist (and membrane channel inhibitor), blocked rapid relaxation (at 100 μM HOCl) and contraction to HOCl. Other antagonists for P2, P2X1, P2Y1 and P2X4 receptors (PPADS, reactive blue 2, NF449, MRS2179 and BX430) did not affect HOCl responses. Relaxation to exogenous ATP was inhibited by 8-SPT but not by suramin suggesting that suramin block of HOCl responses may involve inhibition of membrane channels and endogenous ATP release. Apyrase, which hydrolyzes nucleotides, abolished responses to HOCl, ATP and unexpectedly adenosine. Neither probenecid nor carbenoxelone (connexin and pannexin channel inhibitors) blocked responses to HOCl. Luminescent ATP assay showed that HOCl elicited ATP release from cultures of human coronary artery endothelial cells. These findings advance our understanding of inflammation by showing that HOCl evokes endothelium-dependent vasorelaxation and contraction in coronary arteries which may involve P1 receptors implicating endogenous adenosine, possibly generated from rapid metabolism of ATP released by HOCl.

Keywords: ATP; Adenosine receptor; Coronary artery; Hypochlorous acid; Inflammation; P2 receptor.

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Conflict of interest statement

Declarations. The authors have no relevant financial or non-financial interests to disclose. Ethical approval: This article does not contain any studies with human participants or animals performed by any of the authors. Consent to publish: AB gives consent for this image to be published in Purinergic Signalling. Competing interests: VR is an Associate Editor of Purinergic Signalling.

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