Endothelial function is impaired in conduit arteries of pannexin1 knockout mice

Abstract

Pannexin1 is ubiquitously expressed in vertebrate tissues, but the role it plays in vascular tone regulation remains unclear. We found that Pannexin1 expression level is much higher in the endothelium relative to smooth muscle of saphenous artery. The ability of endothelium-intact arteries for dilation was significantly impaired whereas contractile responses were considerably increased in mice with genetic ablation of Pannexin1. No such increased contractile responses were detected in the endothelium-denuded arteries. Combined, our findings suggest a new function of Pannexin1 as an important player in normal endothelium-dependent regulation of arterial tone, where it facilitates vessel dilation and attenuates constriction.Reviewed by Dr. Armen Mulkidjanian and Dr. Alexander Lobkovsky.

Pannexin 1 facilitates arterial relaxation via an endothelium‐derived hyperpolarization mechanism

“…1 and Table 1 ). We showed as well that Panx1 mRNA localizes predominantly to endothelial cells of the murine saphenous artery [9]. The presence of Panx1 in endothelium was also confirmed by immunohistochemistry in saphenous artery whole mounts (Fig.…”

“…In such arteries the release of ATP via Panx1 hemichannels was shown to be involved in the incremental contractile response during adrenoceptor activation [1]. Conversely, we have shown that in the saphenous artery (a larger resistance‐type vessel) Panx1 is expressed predominantly in the endothelium and Panx1 −/− mice lacking this channel have significantly impaired endothelial function [9]. However, the mechanistic understanding of the role of Panx1 in endothelium‐dependent relaxation remains to be uncovered.…”

Role of connexins and pannexins in cardiovascular physiology

“…Whether or not pannexins play a physiological role in conduit arteries is a matter of debate. It has been reported that conduit arteries from Panx1-deficient animals display slightly reduced endothelium-dependent relaxation [118]. One should, however, consider this conclusion with caution since these measurements have been performed on saphenous artery, which is generally considered to be a muscular resistance artery [119].…”

“…However, contradicting results have been reported as well. First, a study using another muscular resistance artery of Panx1-deficient mice reported enhanced rather than reduced phenylephrine-induced contractions [118]. Moreover, there is also no evidence that Panx1 channels releasing ATP have any role in the constrictor actions of alpha1-adrenoceptor activation of small resistance arteries [151].…”

Pannexins Are Potential New Players in the Regulation of Cerebral Homeostasis during Sleep-Wake Cycle

“…Arteries of Panx1KO mice demonstrate an impaired endothelium-dependent relaxation (Gaynullina et al, 2014) due to the shortage of EDH (Gaynullina et al, 2015). In wild type mice, the EDH-component is inhibited by apyrase and an adenosine receptor antagonist, indicating the involvement of Panx1-mediated ATP release from EC.…”