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Deletion of murine slc29a4 modifies vascular responses to adenosine and 5-hydroxytryptamine in a sexually dimorphic manner.

著者 Wei R , Gust SL , Tandio D , Maheux A , Nguyen KH , Wang J , Bourque S , Plane F , Hammond JR
Physiol Rep.2020 Mar ; 8(5):e14395.
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Equilibrative nucleoside transporter 4 (ENT4), encoded by SLC29A4, mediates the flux of both 5-hydroxytryptamine (5-HT) and adenosine across cell membranes. We hypothesized that loss of ENT4 function in mice would modify the effects of these established regulators of vascular function. Male and female wild-type (WT) and slc29a4-null (ENT4-KO) mice were compared with respect to their hemodynamics and mesenteric vascular function. Male ENT4-KO mice had a complete loss of myogenic tone in their mesenteric resistance arteries. This was accompanied by a decrease in blood flow in the superior mesenteric artery in the male ENT4-KO mice, and a reduced responsiveness to 5-HT. In contrast, endothelium-dependent relaxations of mesenteric arteries from female ENT4-KO mice were more sensitive to Ca -activated K (K ) channel blockade than WT mice. Female ENT4-KO mice also demonstrated an enhanced vasodilatory response to adenosine in vivo that was not seen in males. Ketanserin (5-HT inhibitor) and GR55562 (5-HT inhibitor) decreased 5-HT-induced tone, but only ketanserin inhibited the relaxant effect of 5-HT in mesenteric arteries. 5-HT-evoked increases in tone were elevated in arteries from ENT4-KO mice upon block of endothelial relaxant pathways, with arteries from female ENT4-KO mice showing the greatest increase. Adenosine A receptor expression was decreased, while other adenosine transporter subtypes, as well as adenosine deaminase and adenosine kinase were increased in mesenteric arteries from male, but not female, ENT4-KO mice. These findings indicate that deletion of slc29a4 leads to sex-specific changes in vascular function with significant consequences for regulation of blood flow and pressure by adenosine and 5-HT.
PMID: 32170814 [PubMed - as supplied by publisher]
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