{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T22:58:06Z","timestamp":1774565886810,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T00:00:00Z","timestamp":1701129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["2018R1D1A1B07041820"],"award-info":[{"award-number":["2018R1D1A1B07041820"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["RS-2023-00272628"],"award-info":[{"award-number":["RS-2023-00272628"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["2019R1F1A1061771"],"award-info":[{"award-number":["2019R1F1A1061771"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dapagliflozin, a sodium\u2013glucose co-transporter 2 (SGLT2) inhibitor, is an antidiabetic medication that reduces blood glucose. Although it is well known that dapagliflozin has additional benefits beyond glycemic control, such as reducing blood pressure and lowering the risk of cardiovascular events, no sufficient research data are available on the direct effect of dapagliflozin on cardiovascular function. Thus, in this study, we investigated the direct vascular effect of dapagliflozin on isolated rat coronary arteries. The left descending coronary arteries of 13-week-old male Sprague Dawley rats were cut into segments 2\u20133 mm long and mounted in a multi-wire myography system to measure isometric tension. Dapagliflozin effectively reduced blood vessel constriction induced by U-46619 (500 nM) in coronary arteries regardless of the endothelium. Treatment with an eNOS inhibitor (L-NNA, 100 \u03bcM), sGC inhibitor (ODQ, 5 \u03bcM), or COX inhibitor (indomethacin, 3 \u03bcM) did not affect the vasodilation induced by dapagliflozin. The application of a Ca2+-activated K+ channel (KCa) blocker (TEA, 2 mM), voltage-dependent K+ channel (KV) blocker (4-AP, 2 mM), ATP-sensitive K+ channel blocker (KATP) glibenclamide (3 \u03bcM), and inward-rectifier K+ channel (KIR) blocker (BaCl2, 30 \u03bcM) did not affect the dapagliflozin-induced vasodilation either. The treatment with dapagliflozin decreased contractile responses induced by the addition of Ca2+, which suggested that the extracellular Ca2+ influx was inhibited by dapagliflozin. Treatment with dapagliflozin decreased the phosphorylation level of the 20 kDa myosin light chain (MLC20) in vascular smooth muscle cells. In the present study, we found that dapagliflozin has a significant vasodilatory effect on rat coronary arteries. Our findings suggest a novel pharmacologic approach for the treatment of cardiovascular diseases in diabetic patients through the modulation of Ca2+ homeostasis via dapagliflozin administration.<\/jats:p>","DOI":"10.3390\/ijms242316873","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T07:40:01Z","timestamp":1701157201000},"page":"16873","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Investigating the Cardiovascular Benefits of Dapagliflozin: Vasodilatory Effect on Isolated Rat Coronary Arteries"],"prefix":"10.3390","volume":"24","author":[{"given":"Sooyeon","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Physiology, Yonsei University College of Medicine, 50 Yonseiro, Seodaemun-gu, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8475-3119","authenticated-orcid":false,"given":"Chae Eun","family":"Haam","sequence":"additional","affiliation":[{"name":"Department of Physiology, Yonsei University College of Medicine, 50 Yonseiro, Seodaemun-gu, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seonhee","family":"Byeon","sequence":"additional","affiliation":[{"name":"Department of Physiology, Yonsei University College of Medicine, 50 Yonseiro, Seodaemun-gu, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun Yi","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Physiology, Yonsei University College of Medicine, 50 Yonseiro, Seodaemun-gu, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7115-6358","authenticated-orcid":false,"given":"Soo-Kyoung","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Physiology, Yonsei University College of Medicine, 50 Yonseiro, Seodaemun-gu, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Physiology, Yonsei University College of Medicine, 50 Yonseiro, Seodaemun-gu, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1093\/cvr\/cvy295","article-title":"Potential mechanisms underlying the cardiovascular benefits of sodium glucose cotransporter 2 inhibitors: A systematic review of data from preclinical studies","volume":"115","author":"Chin","year":"2019","journal-title":"Cardiovasc. 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