{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T08:48:15Z","timestamp":1772268495075,"version":"3.50.1"},"reference-count":20,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T00:00:00Z","timestamp":1684972800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81872870"],"award-info":[{"award-number":["81872870"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82070312"],"award-info":[{"award-number":["82070312"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31400983"],"award-info":[{"award-number":["31400983"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Scientific Fund of Heilongjiang Province","award":["H2018011"],"award-info":[{"award-number":["H2018011"]}]},{"name":"Scientific Fund of Heilongjiang Province","award":["LH2022H003"],"award-info":[{"award-number":["LH2022H003"]}]},{"name":"Heilongjiang Province Postdoctoral Foundation","award":["LBH-Q19155"],"award-info":[{"award-number":["LBH-Q19155"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>PFI-3 is a small-molecule inhibitor that targets the bromodomains (BRDs) of Brahma-related gene 1 (BRG1). This monomeric compound, which has high selectivity and potent cellular effects, has recently been developed. Although PFI-3 has been reported as a potential therapeutic agent targeting thrombomodulin, its role in the regulation of vascular function remains unknown. Therefore, we aimed to investigate the impact of PFI-3 on arterial vessel tone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A microvascular tension measurement device (DMT) was utilized to identify alterations in vascular tension within the mesenteric artery. To detect variations in cytosolic [Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ]\n                      <jats:sub>i<\/jats:sub>\n                      , a Fluo-3\/AM fluorescent probe and fluorescence microscope were employed. Additionally, whole-cell patch clamp techniques were utilized to evaluate the activity of L-type voltage-dependent calcium channels (VDCCs) in cultured arterial smooth muscle cells (A10 cells).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PFI-3 exerted a dose-dependent relaxation effect on rat mesenteric arteries with both intact and denuded endothelium after phenylephrine (PE)- and high-K\n                      <jats:sup>+<\/jats:sup>\n                      -induced constriction. PFI-3-induced vasorelaxation was not affected by the presence of L-NAME\/ODQ or K\n                      <jats:sup>+<\/jats:sup>\n                      channel blockers (Gli\/TEA). PFI-3 abolished Ca\n                      <jats:sup>2+<\/jats:sup>\n                      -induced contraction on endothelium-denuded mesenteric arteries preincubated by PE in Ca\n                      <jats:sup>2+<\/jats:sup>\n                      -free solution. Incubation with TG had no impact on PFI-3-induced vasorelaxation pre-contracted by PE. PFI-3 reduced Ca\n                      <jats:sup>2+<\/jats:sup>\n                      -induced contraction on endothelium-denuded mesenteric arteries pre-incubated by KCl (60\u00a0mM) in Ca\n                      <jats:sup>2+<\/jats:sup>\n                      -free solution. PFI-3 declined extracellular calcium influx in A10 cells detected by Fluo-3\/AM fluorescent probe and fluorescence microscope. Furthermore, we observed that PFI-3 decreased the current densities of L-type VDCC by whole-cell patch clamp techniques.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      PFI-3 blunted PE and high K\n                      <jats:sup>+<\/jats:sup>\n                      -induced vasoconstriction independent of endothelium on rat mesenteric artery. The vasodilatory effect of PFI-3 may be attributed to its inhibition of VDCCs and receptor-operated calcium channels (ROCCs) on vascular smooth muscle cells (VSMCs).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.7717\/peerj.15407","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T04:19:08Z","timestamp":1684988348000},"page":"e15407","source":"Crossref","is-referenced-by-count":0,"title":["PFI-3 induces vasorelaxation with potency to reduce extracellular calcium influx in rat mesenteric artery"],"prefix":"10.7717","volume":"11","author":[{"given":"Jing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacology (The Key Laboratory of Cardiovascular Research, Ministry of Education) at College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang Province, 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