Nitric Oxide and Small and Intermediate Calcium-Activated Potassium Channels Mediate the Vasodilation Induced by Apigenin in the Resistance Vessels of Hypertensive Rats
Background: Apigenin (4′,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...
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MDPI AG
2024-11-01
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| author | Lislaine Maria Klider Maria Luiza Fidelis da Silva Gustavo Ratti da Silva João Ricardo Cray da Costa Marcia Alessandra Arantes Marques Emerson Luiz Botelho Lourenço Francislaine Aparecida dos Reis Lívero Jane Manfron Arquimedes Gasparotto Junior |
| author_facet | Lislaine Maria Klider Maria Luiza Fidelis da Silva Gustavo Ratti da Silva João Ricardo Cray da Costa Marcia Alessandra Arantes Marques Emerson Luiz Botelho Lourenço Francislaine Aparecida dos Reis Lívero Jane Manfron Arquimedes Gasparotto Junior |
| author_sort | Lislaine Maria Klider |
| collection | DOAJ |
| description | Background: Apigenin (4′,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. |
| format | Article |
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| institution | OA Journals |
| issn | 1420-3049 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj-art-cfd0ec0ab8e04b718b3bbca7affbd9e62025-08-20T02:04:59ZengMDPI AGMolecules1420-30492024-11-012922542510.3390/molecules29225425Nitric Oxide and Small and Intermediate Calcium-Activated Potassium Channels Mediate the Vasodilation Induced by Apigenin in the Resistance Vessels of Hypertensive RatsLislaine Maria Klider0Maria Luiza Fidelis da Silva1Gustavo Ratti da Silva2João Ricardo Cray da Costa3Marcia Alessandra Arantes Marques4Emerson Luiz Botelho Lourenço5Francislaine Aparecida dos Reis Lívero6Jane Manfron7Arquimedes Gasparotto Junior8Laboratory of Cardiometabolic Pharmacology, Postgraduate Program in Pharmacology (UFPR), Federal University of Paraná, Curitiba 81531-980, PR, BrazilLaboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados (UFGD), Dourados 79804-970, MS, BrazilLaboratory of Preclinical Research of Natural Products, Post Graduate Program in Animal Science with Emphasis on Bioactive Products, Paranaense University, Umuarama 87502-210, PR, BrazilLaboratory of Preclinical Research of Natural Products, Post-Graduate Program in Medicinal Plants and Phytotherapeutics in Basic Attention, Paranaense University, Umuarama 87502-210, PR, BrazilLaboratory of Preclinical Research of Natural Products, Post Graduate Program in Animal Science with Emphasis on Bioactive Products, Paranaense University, Umuarama 87502-210, PR, BrazilLaboratory of Preclinical Research of Natural Products, Post Graduate Program in Animal Science with Emphasis on Bioactive Products, Paranaense University, Umuarama 87502-210, PR, BrazilLaboratory of Cardiometabolic Pharmacology, Postgraduate Program in Pharmacology (UFPR), Federal University of Paraná, Curitiba 81531-980, PR, BrazilGraduate Program in Pharmaceutical Sciences, State University of Ponta Grossa, Ponta Grossa 84010-330, PR, BrazilLaboratory of Cardiometabolic Pharmacology, Postgraduate Program in Pharmacology (UFPR), Federal University of Paraná, Curitiba 81531-980, PR, BrazilBackground: Apigenin (4′,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.https://www.mdpi.com/1420-3049/29/22/5425apigeninflavonemesenteric vascular bedpotassium channelvasodilation |
| spellingShingle | Lislaine Maria Klider Maria Luiza Fidelis da Silva Gustavo Ratti da Silva João Ricardo Cray da Costa Marcia Alessandra Arantes Marques Emerson Luiz Botelho Lourenço Francislaine Aparecida dos Reis Lívero Jane Manfron Arquimedes Gasparotto Junior Nitric Oxide and Small and Intermediate Calcium-Activated Potassium Channels Mediate the Vasodilation Induced by Apigenin in the Resistance Vessels of Hypertensive Rats Molecules apigenin flavone mesenteric vascular bed potassium channel vasodilation |
| title | Nitric Oxide and Small and Intermediate Calcium-Activated Potassium Channels Mediate the Vasodilation Induced by Apigenin in the Resistance Vessels of Hypertensive Rats |
| title_full | Nitric Oxide and Small and Intermediate Calcium-Activated Potassium Channels Mediate the Vasodilation Induced by Apigenin in the Resistance Vessels of Hypertensive Rats |
| title_fullStr | Nitric Oxide and Small and Intermediate Calcium-Activated Potassium Channels Mediate the Vasodilation Induced by Apigenin in the Resistance Vessels of Hypertensive Rats |
| title_full_unstemmed | Nitric Oxide and Small and Intermediate Calcium-Activated Potassium Channels Mediate the Vasodilation Induced by Apigenin in the Resistance Vessels of Hypertensive Rats |
| title_short | Nitric Oxide and Small and Intermediate Calcium-Activated Potassium Channels Mediate the Vasodilation Induced by Apigenin in the Resistance Vessels of Hypertensive Rats |
| title_sort | nitric oxide and small and intermediate calcium activated potassium channels mediate the vasodilation induced by apigenin in the resistance vessels of hypertensive rats |
| topic | apigenin flavone mesenteric vascular bed potassium channel vasodilation |
| url | https://www.mdpi.com/1420-3049/29/22/5425 |
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