3',4'-Dihydroxyflavonol reduces vascular contraction through Ca²⁺ desensitization in permeabilized rat mesenteric artery

Abstract

3',4'-Dihydroxyflavonol (DiOHF) exerts endothelium-independent relaxation in rat aortic rings. In this study, we hypothesized that DiOHF reduces vascular contraction through Ca²⁺ desensitization in permeabilized third-order branches of rat mesenteric arteries. The third-order branches of rat mesenteric arteries were permeabilized with β-escin and subjected to tension measurement. Cumulative addition of phenylephrine (0.3-30 μM) produced concentration-dependent vascular contraction of endothelium-intact and endothelium-denuded arterial rings, which were inhibited by pretreatment with DiOHF (10, 30, or 100 μM). In addition, DiOHF dose-dependently decreased vascular contractions induced by 3.0 μM phenylephrine. β-Escin-permeabilized third-order branches of mesenteric arteries were contracted with Ca²⁺, NaF, or guanosine-5'-(γ-thio)triphosphate (GTPγS) 30 min after pretreatment with DiOHF or vehicle. Pretreatment with DiOHF for 30 min inhibited vascular contraction induced by cumulative additions of Ca²⁺ (pCa 9.0-6.0) or NaF (4.0-16.0 mM) in permeabilized arterial rings. Cumulative addition of DiOHF also reduced vascular contraction induced by Ca²⁺-controlled solution of pCa 6.0, 16.0 mM NaF, or 100 μM GTPγS in permeabilized arterial rings. DiOHF inhibited the increase in vascular tension provoked by calyculin A, even though it did not affect vascular tension already produced by calyculin A. DiOHF accelerated the relaxation induced by rapidly lowering Ca²⁺. DiOHF reduced vascular contraction through Ca²⁺ desensitization in permeabilized third-order branches of rat mesenteric arteries. These results suggest that DiOHF may have a therapeutic potential in the treatment of cardiovascular diseases.