Nitric Oxide and Small and Intermediate Calcium-Activated Potassium Channels Mediate the Vasodilation Induced by Apigenin in the Resistance Vessels of Hypertensive Rats
2024
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
Background: Apigenin (4&prime:,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.
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