Nitric Oxide and Small and Intermediate Calcium-Activated Potassium Channels Mediate the Vasodilation Induced by Apigenin in the Resistance Vessels of Hypertensive Rats.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, c1995-
    • Subject Terms:
      Apigenin*/pharmacology ; Vasodilation*/drug effects ; Nitric Oxide*/metabolism ; Rats, Inbred SHR*; Animals ; Rats ; Male ; Hypertension/drug therapy ; Hypertension/metabolism ; Potassium Channel Blockers/pharmacology ; Small-Conductance Calcium-Activated Potassium Channels/metabolism ; Small-Conductance Calcium-Activated Potassium Channels/antagonists & inhibitors ; Mesenteric Arteries/drug effects ; Mesenteric Arteries/metabolism ; Intermediate-Conductance Calcium-Activated Potassium Channels/metabolism ; Intermediate-Conductance Calcium-Activated Potassium Channels/antagonists & inhibitors ; Apamin/pharmacology ; Potassium Channels, Calcium-Activated/metabolism ; Vascular Resistance/drug effects ; Tetraethylammonium/pharmacology
    • Abstract:
      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.
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    • Contributed Indexing:
      Keywords: apigenin; flavone; mesenteric vascular bed; potassium channel; vasodilation
    • Accession Number:
      7V515PI7F6 (Apigenin)
      31C4KY9ESH (Nitric Oxide)
      0 (Potassium Channel Blockers)
      0 (Small-Conductance Calcium-Activated Potassium Channels)
      0 (Intermediate-Conductance Calcium-Activated Potassium Channels)
      24345-16-2 (Apamin)
      0 (Potassium Channels, Calcium-Activated)
      66-40-0 (Tetraethylammonium)
    • Publication Date:
      Date Created: 20241127 Date Completed: 20241127 Latest Revision: 20241130
    • Publication Date:
      20241202
    • Accession Number:
      PMC11597377
    • Accession Number:
      10.3390/molecules29225425
    • Accession Number:
      39598814