{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T17:13:12Z","timestamp":1773681192308,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Apoio ao Desenvolvimento do Ensino, Ci\u00eancia e Tecnologia do Estado de Mato Grosso do Sul (FUNDECT, Brazil)","award":["71\/700.135\/2018"],"award-info":[{"award-number":["71\/700.135\/2018"]}]},{"name":"Funda\u00e7\u00e3o de Apoio ao Desenvolvimento do Ensino, Ci\u00eancia e Tecnologia do Estado de Mato Grosso do Sul (FUNDECT, Brazil)","award":["83\/013.186\/2023"],"award-info":[{"award-number":["83\/013.186\/2023"]}]},{"name":"Funda\u00e7\u00e3o de Apoio ao Desenvolvimento do Ensino, Ci\u00eancia e Tecnologia do Estado de Mato Grosso do Sul (FUNDECT, Brazil)","award":["407685\/2018-9"],"award-info":[{"award-number":["407685\/2018-9"]}]},{"name":"Funda\u00e7\u00e3o de Apoio ao Desenvolvimento do Ensino, Ci\u00eancia e Tecnologia do Estado de Mato Grosso do Sul (FUNDECT, Brazil)","award":["150258\/2023-2"],"award-info":[{"award-number":["150258\/2023-2"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq, Brazil)","award":["71\/700.135\/2018"],"award-info":[{"award-number":["71\/700.135\/2018"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq, Brazil)","award":["83\/013.186\/2023"],"award-info":[{"award-number":["83\/013.186\/2023"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq, Brazil)","award":["407685\/2018-9"],"award-info":[{"award-number":["407685\/2018-9"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq, Brazil)","award":["150258\/2023-2"],"award-info":[{"award-number":["150258\/2023-2"]}]},{"name":"Coordenadoria de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES, Brazil)","award":["71\/700.135\/2018"],"award-info":[{"award-number":["71\/700.135\/2018"]}]},{"name":"Coordenadoria de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES, Brazil)","award":["83\/013.186\/2023"],"award-info":[{"award-number":["83\/013.186\/2023"]}]},{"name":"Coordenadoria de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES, Brazil)","award":["407685\/2018-9"],"award-info":[{"award-number":["407685\/2018-9"]}]},{"name":"Coordenadoria de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES, Brazil)","award":["150258\/2023-2"],"award-info":[{"award-number":["150258\/2023-2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Background: Apigenin (4\u2032,5,7-trihydroxyflavone), a flavonoid with potential cardiovascular benefits, has unclear mechanisms of action. This study investigates its effects on vascular function in Spontaneously Hypertensive Rats (SHRs). Methods: Mesenteric vascular beds (MVBs) were isolated from SHRs and perfused with increasing doses of apigenin after pre-contraction with phenylephrine. To explore the mechanisms, different MVBs were pre-perfused with antagonists and inhibitors, including indomethacin, L-NAME, and potassium channel blockers (tetraethylammonium, a non-specific potassium channel blocker; glibenclamide, an ATP-sensitive potassium channel blocker; 4-aminopyridine, a voltage-gated potassium channel blocker; charybdotoxin a selective intermediate-conductance calcium-activated potassium channel blocker; and apamin, a selective small-conductance calcium-activated potassium channel blocker). Results: Apigenin induced a dose-dependent reduction in perfusion pressure in MVBs with intact endothelium, an effect abolished by endothelium removal. L-NAME reduced apigenin-induced vasodilation by approximately 40%. The vasodilatory effect was blocked by potassium chloride and tetraethylammonium. The inhibition of small and intermediate calcium-activated potassium channels with charybdotoxin and apamin reduced apigenin-induced vasodilation by 50%, and a combination of these blockers with L-NAME completely inhibited the effect. Conclusions: Apigenin promotes vasodilation in resistance arteries through endothelial nitric oxide and calcium-activated potassium channels. These findings suggest that apigenin could have therapeutic potential in cardiovascular disease, warranting further clinical research.<\/jats:p>","DOI":"10.3390\/molecules29225425","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T07:51:15Z","timestamp":1732002675000},"page":"5425","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Nitric Oxide and Small and Intermediate Calcium-Activated Potassium Channels Mediate the Vasodilation Induced by Apigenin in the Resistance Vessels of Hypertensive Rats"],"prefix":"10.3390","volume":"29","author":[{"given":"Lislaine Maria","family":"Klider","sequence":"first","affiliation":[{"name":"Laboratory of Cardiometabolic Pharmacology, Postgraduate Program in Pharmacology (UFPR), Federal University of Paran\u00e1, Curitiba 81531-980, PR, Brazil"},{"name":"Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados (UFGD), Dourados 79804-970, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Luiza Fidelis","family":"da Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados (UFGD), Dourados 79804-970, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7224-8898","authenticated-orcid":false,"given":"Gustavo Ratti","family":"da Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical Research of Natural Products, Post Graduate Program in Animal Science with Emphasis on Bioactive Products, Paranaense University, Umuarama 87502-210, PR, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o Ricardo Cray","family":"da Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical Research of Natural Products, Post-Graduate Program in Medicinal Plants and Phytotherapeutics in Basic Attention, Paranaense University, Umuarama 87502-210, PR, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcia Alessandra Arantes","family":"Marques","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical Research of Natural Products, Post Graduate Program in Animal Science with Emphasis on Bioactive Products, Paranaense University, Umuarama 87502-210, PR, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1798-7871","authenticated-orcid":false,"given":"Emerson Luiz Botelho","family":"Louren\u00e7o","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical Research of Natural Products, Post Graduate Program in Animal Science with Emphasis on Bioactive Products, Paranaense University, Umuarama 87502-210, PR, Brazil"},{"name":"Laboratory of Preclinical Research of Natural Products, Post-Graduate Program in Medicinal Plants and Phytotherapeutics in Basic Attention, Paranaense University, Umuarama 87502-210, PR, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francislaine Aparecida dos Reis","family":"L\u00edvero","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiometabolic Pharmacology, Postgraduate Program in Pharmacology (UFPR), Federal University of Paran\u00e1, Curitiba 81531-980, PR, Brazil"},{"name":"Laboratory of Preclinical Research of Natural Products, Post Graduate Program in Animal Science with Emphasis on Bioactive Products, Paranaense University, Umuarama 87502-210, PR, Brazil"},{"name":"Laboratory of Preclinical Research of Natural Products, Post-Graduate Program in Medicinal Plants and Phytotherapeutics in Basic Attention, Paranaense University, Umuarama 87502-210, PR, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1873-2253","authenticated-orcid":false,"given":"Jane","family":"Manfron","sequence":"additional","affiliation":[{"name":"Graduate Program in Pharmaceutical Sciences, State University of Ponta Grossa, Ponta Grossa 84010-330, PR, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3433-5098","authenticated-orcid":false,"given":"Arquimedes","family":"Gasparotto Junior","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiometabolic Pharmacology, Postgraduate Program in Pharmacology (UFPR), Federal University of Paran\u00e1, Curitiba 81531-980, PR, Brazil"},{"name":"Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados (UFGD), Dourados 79804-970, MS, Brazil"},{"name":"Laboratory of Preclinical Research of Natural Products, Post-Graduate Program in Medicinal Plants and Phytotherapeutics in Basic Attention, Paranaense University, Umuarama 87502-210, PR, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Salehi, B., Venditti, A., Sharifi-Rad, M., Kr\u0119giel, D., Sharifi-Rad, J., Durazzo, A., Lucarini, M., Santini, A., Souto, E.B., and Novellino, E. 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