Objective To investigate the vasodilatory effect of luteolin on isolated denuded-endothelium rat thoracic aorta(DRTA)vascular rings,and the mechanistic role of the Kv7 ion channel.Methods The tension of DRTA vascular rings was measured using an ex vivo tissue perfusion muscle-tone detection system.DRTA vascular rings were pre-contracted with 60 mmol/L KCl or 0.3 μmol/L U46619,and the effect of luteolin on vascular-ring relaxation was observed at 1,3,10,30,100 and 300 μmol/L.The effects of 4-AP,XE-991,and ML213 on luteolin-induced vasodilation were also observed.The effect of luteolin on KCNQ1-KCNQ5 expression in the thoracic aorta was detected by real-time fluorescence quantitative polymerase chain reaction.Expression levels of Kv7.1 and Kv7.4 proteins in the DRTA were detected by Western blot.Results(1)The luteolin-induced maximum vasodilation rates in DRTA pre-contracted with 60 mmol/L KCl and 0.3 μmol/L U46619 were(97.67±8.51)％and(98.42±9.76)％,respectively.The vasodilation effect was concentration-dependent(P＜0.05).(2)4-AP(3 mmol/L)significantly reduced the vasodilatory effect of luteolin on DRTA vascular rings at 10,30,and 100 μmol/L(P＜0.05),and XE-991(3 μmol/L)significantly reduced the effect of luteolin at 30 and 100 μmol/L(P＜0.05),while ML213(1 μmol/L)significantly enhanced the vasodilatory effect of luteolin at 3,10,and 30 μmol/L(P＜0.05).(3)The relative gene expression levels of each subtype of Kv7 channel in normal DRTA were KCNQ1＞KCNQ5＞KCNQ4＞KCNQ3＞KCNQ2,with KCNQ1 being the most highly expressed.(4)Luteolin significantly enhanced the expression levels of KCNQ1 at 3,10,30,and 100 μmol/L,KCNQ2 at 1,3,10,30,and 100 μmol/L(P＜0.05),KCNQ3 at 3,10,30,and 100 μmol/L,and KCNQ4 at 10,30,and 100 μmol/L(P＜0.05),but did not significantly enhance the expression of KCNQ5 at 1,3,10,30,or 100 μmol/L(P＞0.05).(5)Luteolin significantly increased the expression of Kv7.1 protein in DRTA at 3,10,30,and 100 μmol/L(P＜0.05)and the expression of Kv7.4 at 10,30,and 100 μmol/L(P＜0.05).Conclusions Luteolin-induced dilation of DRTA vascular rings may be related to the enhanced gene expression of KCNQ1-4 and increased expression of Kv7.1 and Kv7.4 channel proteins.

Objective To investigate the vasodilatory effect of luteolin on isolated denuded-endothelium rat thoracic aorta(DRTA)vascular rings,and the mechanistic role of the Kv7 ion channel.Methods The tension of DRTA vascular rings was measured using an ex vivo tissue perfusion muscle-tone detection system.DRTA vascular rings were pre-contracted with 60 mmol/L KCl or 0.3 μmol/L U46619,and the effect of luteolin on vascular-ring relaxation was observed at 1,3,10,30,100 and 300 μmol/L.The effects of 4-AP,XE-991,and ML213 on luteolin-induced vasodilation were also observed.The effect of luteolin on KCNQ1-KCNQ5 expression in the thoracic aorta was detected by real-time fluorescence quantitative polymerase chain reaction.Expression levels of Kv7.1 and Kv7.4 proteins in the DRTA were detected by Western blot.Results(1)The luteolin-induced maximum vasodilation rates in DRTA pre-contracted with 60 mmol/L KCl and 0.3 μmol/L U46619 were(97.67±8.51)％and(98.42±9.76)％,respectively.The vasodilation effect was concentration-dependent(P＜0.05).(2)4-AP(3 mmol/L)significantly reduced the vasodilatory effect of luteolin on DRTA vascular rings at 10,30,and 100 μmol/L(P＜0.05),and XE-991(3 μmol/L)significantly reduced the effect of luteolin at 30 and 100 μmol/L(P＜0.05),while ML213(1 μmol/L)significantly enhanced the vasodilatory effect of luteolin at 3,10,and 30 μmol/L(P＜0.05).(3)The relative gene expression levels of each subtype of Kv7 channel in normal DRTA were KCNQ1＞KCNQ5＞KCNQ4＞KCNQ3＞KCNQ2,with KCNQ1 being the most highly expressed.(4)Luteolin significantly enhanced the expression levels of KCNQ1 at 3,10,30,and 100 μmol/L,KCNQ2 at 1,3,10,30,and 100 μmol/L(P＜0.05),KCNQ3 at 3,10,30,and 100 μmol/L,and KCNQ4 at 10,30,and 100 μmol/L(P＜0.05),but did not significantly enhance the expression of KCNQ5 at 1,3,10,30,or 100 μmol/L(P＞0.05).(5)Luteolin significantly increased the expression of Kv7.1 protein in DRTA at 3,10,30,and 100 μmol/L(P＜0.05)and the expression of Kv7.4 at 10,30,and 100 μmol/L(P＜0.05).Conclusions Luteolin-induced dilation of DRTA vascular rings may be related to the enhanced gene expression of KCNQ1-4 and increased expression of Kv7.1 and Kv7.4 channel proteins.