{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T11:06:32Z","timestamp":1773399992108,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81973510"],"award-info":[{"award-number":["81973510"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Key Natural Science Research Projects of Anhui Universities","award":["2023AH050842"],"award-info":[{"award-number":["2023AH050842"]}]},{"name":"Clinical Research Project of Anhui University of Traditional Chinese Medicine in 2024","award":["2024LC055"],"award-info":[{"award-number":["2024LC055"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>To explore the mechanism of action of CBS-derived H2S in inducing cerebral vasodilation and activating BKCa channels. Sprague\u2013Dawley (SD) rat middle cerebral arteries (MCA) were isolated from rat brains, and a pressure myography system was used to measure the effects of different concentrations of L-cysteine (L-Cys, 1 \u00d7 10\u22125.5 to 1 \u00d7 10\u22123.5 mol\/L), a substrate for cystathionine-\u03b2-synthase (CBS)\u2014a hydrogen sulfide (H2S)-producing enzyme. Additionally, the effects of pretreatment with the CBS inhibitor amino-oxoacetate (AOAA, 1 mmol\/L), the vascular endothelial growth factor receptor 2 inhibitor semaxanib (SU5416, 10 \u03bcmol\/L), and the large-conductance calcium-activated potassium (BKCa) channel blocker iberiotoxin (IBTX, 100 nmol\/L) were investigated to determine their impacts on CBS-derived H2S-induced vasodilation. Acute digestion of rat vascular smooth muscle cells (VSMCs) was performed, and whole-cell patch-clamp techniques were used to measure current changes in neurons or astrocytes (ASTs), as well as acutely digested VSMCs, in the presence of L-Cys, AOAA (1 mmol\/L), SU5416 (10 \u03bcmol\/L), and IBTX (100 nmol\/L). Additionally, neurons or ASTs were co-cultured with VSMCs to determine CBS-derived H2S levels. Neurons or ASTs co-incubated with blood vessels and then treated with L-Cys produced H2S, which exhibited a concentration-dependent dilatory effect on middle cerebral artery occlusion (MCA) pre-contracted with 100 nmol\/L U46619 (p &lt; 0.01). However, the addition of AOAA significantly attenuated this dilatory effect (p &lt; 0.01). SU5416 and IBTX significantly inhibited cerebral vascular dilation (p &lt; 0.01). H2S produced by adding L-Cys after co-incubation of neurons or ASTs with VSMCs significantly increased BKCa channel current (p &lt; 0.01). However, this effect was significantly attenuated after adding AOAA (p &lt; 0.01). SU5416 and IBTX significantly inhibited the activation of BKCa channels (p &lt; 0.01). Wild-type rat neurons or astrocytes (ASTs) were co-cultured with CSE(Cystathionine \u03b3-lyase)-knockout vascular smooth muscle cells (VSMCs-CSE KO); the addition of L-Cys significantly increased hydrogen sulfide (H2S) levels in the co-culture system (p &lt; 0.01), while the addition of AOAA reduced H2S production (p &lt; 0.01). However, the addition of SU5416 had no statistical significance. Neurogenic H2S, the H2S produced by neurons and ASTs, could induce cerebral vasodilation in rats via VEGFR2(Vascular Endothelial Growth Factor Receptor 2)-mediated activation of BKCa channels in the smooth muscle cells.<\/jats:p>","DOI":"10.3390\/cimb48030284","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T17:25:59Z","timestamp":1772817959000},"page":"284","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Activation of BKCa Channels in Rat Cerebrovascular Smooth Muscle Cells and Vasodilation Induced by Neurogenic H2S and Its Relationship with VEGFR2"],"prefix":"10.3390","volume":"48","author":[{"given":"Shan","family":"Wang","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Anhui Medical University, Hefei 230032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Anhui Medical University, Hefei 230032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-Rong","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Anhui Medical University, Hefei 230032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Anhui Medical University, Hefei 230032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Yue","family":"Wen","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Anhui Medical University, Hefei 230032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Wu","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Anhui Medical University, Hefei 230032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuo","family":"Chen","sequence":"additional","affiliation":[{"name":"The Experimental Research Center, Anhui University of Chinese Medicine, Hefei 230038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"117873","DOI":"10.1016\/j.ejmech.2025.117873","article-title":"Discovery of a potential anti-ischemic stroke agent by suppressing ferroptosis through the ATF3\/SLC7A11\/GPX4 pathway","volume":"296","author":"Kong","year":"2025","journal-title":"Eur. 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