Investigating the Cardiovascular Benefits of Dapagliflozin: Vasodilatory Effect on Isolated Rat Coronary Arteries
Dapagliflozin, a sodium–glucose 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,...
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MDPI AG
2023-11-01
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| Series: | International Journal of Molecular Sciences |
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| author | Sooyeon Choi Chae Eun Haam Seonhee Byeon Eun Yi Oh Soo-Kyoung Choi Young-Ho Lee |
| author_facet | Sooyeon Choi Chae Eun Haam Seonhee Byeon Eun Yi Oh Soo-Kyoung Choi Young-Ho Lee |
| author_sort | Sooyeon Choi |
| collection | DOAJ |
| description | Dapagliflozin, a sodium–glucose 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 2–3 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 μM), sGC inhibitor (ODQ, 5 μM), or COX inhibitor (indomethacin, 3 μM) did not affect the vasodilation induced by dapagliflozin. The application of a Ca<sup>2+</sup>-activated K<sup>+</sup> channel (K<sub>Ca</sub>) blocker (TEA, 2 mM), voltage-dependent K<sup>+</sup> channel (K<sub>V</sub>) blocker (4-AP, 2 mM), ATP-sensitive K<sup>+</sup> channel blocker (K<sub>ATP</sub>) glibenclamide (3 μM), and inward-rectifier K<sup>+</sup> channel (K<sub>IR</sub>) blocker (BaCl<sub>2</sub>, 30 μM) did not affect the dapagliflozin-induced vasodilation either. The treatment with dapagliflozin decreased contractile responses induced by the addition of Ca<sup>2+</sup>, which suggested that the extracellular Ca<sup>2+</sup> influx was inhibited by dapagliflozin. Treatment with dapagliflozin decreased the phosphorylation level of the 20 kDa myosin light chain (MLC<sub>20</sub>) 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 Ca<sup>2+</sup> homeostasis via dapagliflozin administration. |
| first_indexed | 2024-03-09T01:50:26Z |
| format | Article |
| id | doaj.art-fe0ce8cd20334c288a8ec13020e2255c |
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| language | English |
| last_indexed | 2024-03-09T01:50:26Z |
| publishDate | 2023-11-01 |
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| spelling | doaj.art-fe0ce8cd20334c288a8ec13020e2255c2023-12-08T15:17:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124231687310.3390/ijms242316873Investigating the Cardiovascular Benefits of Dapagliflozin: Vasodilatory Effect on Isolated Rat Coronary ArteriesSooyeon Choi0Chae Eun Haam1Seonhee Byeon2Eun Yi Oh3Soo-Kyoung Choi4Young-Ho Lee5Department of Physiology, Yonsei University College of Medicine, 50 Yonseiro, Seodaemun-gu, Seoul 03722, Republic of KoreaDepartment of Physiology, Yonsei University College of Medicine, 50 Yonseiro, Seodaemun-gu, Seoul 03722, Republic of KoreaDepartment of Physiology, Yonsei University College of Medicine, 50 Yonseiro, Seodaemun-gu, Seoul 03722, Republic of KoreaDepartment of Physiology, Yonsei University College of Medicine, 50 Yonseiro, Seodaemun-gu, Seoul 03722, Republic of KoreaDepartment of Physiology, Yonsei University College of Medicine, 50 Yonseiro, Seodaemun-gu, Seoul 03722, Republic of KoreaDepartment of Physiology, Yonsei University College of Medicine, 50 Yonseiro, Seodaemun-gu, Seoul 03722, Republic of KoreaDapagliflozin, a sodium–glucose 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 2–3 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 μM), sGC inhibitor (ODQ, 5 μM), or COX inhibitor (indomethacin, 3 μM) did not affect the vasodilation induced by dapagliflozin. The application of a Ca<sup>2+</sup>-activated K<sup>+</sup> channel (K<sub>Ca</sub>) blocker (TEA, 2 mM), voltage-dependent K<sup>+</sup> channel (K<sub>V</sub>) blocker (4-AP, 2 mM), ATP-sensitive K<sup>+</sup> channel blocker (K<sub>ATP</sub>) glibenclamide (3 μM), and inward-rectifier K<sup>+</sup> channel (K<sub>IR</sub>) blocker (BaCl<sub>2</sub>, 30 μM) did not affect the dapagliflozin-induced vasodilation either. The treatment with dapagliflozin decreased contractile responses induced by the addition of Ca<sup>2+</sup>, which suggested that the extracellular Ca<sup>2+</sup> influx was inhibited by dapagliflozin. Treatment with dapagliflozin decreased the phosphorylation level of the 20 kDa myosin light chain (MLC<sub>20</sub>) 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 Ca<sup>2+</sup> homeostasis via dapagliflozin administration.https://www.mdpi.com/1422-0067/24/23/16873SGLT2 inhibitordapagliflozincoronary arteryrelaxation |
| spellingShingle | Sooyeon Choi Chae Eun Haam Seonhee Byeon Eun Yi Oh Soo-Kyoung Choi Young-Ho Lee Investigating the Cardiovascular Benefits of Dapagliflozin: Vasodilatory Effect on Isolated Rat Coronary Arteries International Journal of Molecular Sciences SGLT2 inhibitor dapagliflozin coronary artery relaxation |
| title | Investigating the Cardiovascular Benefits of Dapagliflozin: Vasodilatory Effect on Isolated Rat Coronary Arteries |
| title_full | Investigating the Cardiovascular Benefits of Dapagliflozin: Vasodilatory Effect on Isolated Rat Coronary Arteries |
| title_fullStr | Investigating the Cardiovascular Benefits of Dapagliflozin: Vasodilatory Effect on Isolated Rat Coronary Arteries |
| title_full_unstemmed | Investigating the Cardiovascular Benefits of Dapagliflozin: Vasodilatory Effect on Isolated Rat Coronary Arteries |
| title_short | Investigating the Cardiovascular Benefits of Dapagliflozin: Vasodilatory Effect on Isolated Rat Coronary Arteries |
| title_sort | investigating the cardiovascular benefits of dapagliflozin vasodilatory effect on isolated rat coronary arteries |
| topic | SGLT2 inhibitor dapagliflozin coronary artery relaxation |
| url | https://www.mdpi.com/1422-0067/24/23/16873 |
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