Nitric Oxide and Small and Intermediate Calcium-Activated Potassium Channels Mediate the Vasodilation Induced by Apigenin in the Resistance Vessels of Hypertensive Rats
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
Affiliations
Lislaine Maria Klider
Laboratory of Cardiometabolic Pharmacology, Postgraduate Program in Pharmacology (UFPR), Federal University of Paraná, Curitiba 81531-980, PR, Brazil
Maria Luiza Fidelis da Silva
Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados (UFGD), Dourados 79804-970, MS, Brazil
Gustavo Ratti da Silva
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
João Ricardo Cray da Costa
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
Marcia Alessandra Arantes Marques
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
Emerson Luiz Botelho Lourenço
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
Francislaine Aparecida dos Reis Lívero
Laboratory of Cardiometabolic Pharmacology, Postgraduate Program in Pharmacology (UFPR), Federal University of Paraná, Curitiba 81531-980, PR, Brazil
Jane Manfron
Graduate Program in Pharmaceutical Sciences, State University of Ponta Grossa, Ponta Grossa 84010-330, PR, Brazil
Arquimedes Gasparotto Junior
Laboratory of Cardiometabolic Pharmacology, Postgraduate Program in Pharmacology (UFPR), Federal University of Paraná, Curitiba 81531-980, PR, Brazil
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.
