{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:01:24Z","timestamp":1790740884528,"version":"4.1.0"},"reference-count":26,"publisher":"The Korean Society of Anesthesiologists","issue":"5","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1F1A1062363"],"award-info":[{"award-number":["2021R1F1A1062363"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1I1A3040332"],"award-info":[{"award-number":["2021R1I1A3040332"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002701","name":"Ministry of Education","doi-asserted-by":"publisher","award":["IRIS RS-2023-00238572"],"award-info":[{"award-number":["IRIS RS-2023-00238572"]}],"id":[{"id":"10.13039\/501100002701","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ekja.org"],"crossmark-restriction":true},"short-container-title":["Korean J Anesthesiol"],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:p>Background: High-dose insulin and euglycemic therapy are widely used to treat calcium channel blocker toxicity. However, the effect of insulin on vasodilation evoked by the dihydropyridine calcium channel blocker amlodipine remains unknown. This study examined the effect of insulin on amlodipine-induced vasodilation in isolated rat aortas with specific emphasis on mechanisms associated with nitric oxide (NO).Methods: The study assessed the roles of NW-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor; methylene blue, a general guanylate cyclase suppressor; 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a selective inhibitor of NO-sensitive guanylate cyclase; and endothelial removal in modulating the NO-dependent signaling cascade underlying amlodipine-induced vasodilation. This study explored how insulin and various pharmacological inhibitors influenced the vasodilatory effects of amlodipine and verapamil in rat aortic tissues with or without an intact endothelium. Results: In aortas with intact endothelium, amlodipine-induced relaxation was significantly suppressed by L-NAME, methylene blue, and ODQ. Insulin enhanced amlodipine-induced vasodilation in endothelium-intact aortas, whereas it had no effect on the vasodilatory response to amlodipine in endothelium-denuded aortas. Moreover, L-NAME, methylene blue, and ODQ eliminated insulin-mediated augmentation of amlodipine-induced vasodilation in endothelium-intact aortas. However, in endothelium-intact aortas, insulin exhibited no impact on the vasodilatory effects triggered by verapamil. Amlodipine increased endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells (HUVECs). Additionally, combined treatment with insulin and amlodipine further increased amlodipine-induced eNOS phosphorylation in HUVECs. Conclusions: These findings suggest that insulin contributes to the amplification of amlodipine\u2019s NO-dependent vasodilatory response in aortas, which appears to be mediated by increased NO production.<\/jats:p>","DOI":"10.4097\/kja.25416","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T09:09:59Z","timestamp":1757322599000},"page":"542-554","update-policy":"https:\/\/doi.org\/10.4097\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Insulin augments vasodilatory response elicited by amlodipine via nitric oxide-dependent vasodilation in isolated rat aortas"],"prefix":"10.4097","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6047-633X","authenticated-orcid":true,"given":"Soo 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