Effects Of Tetramethylpyrazine On Vascular Tone Of Placental Arteries From Preeclampsia Patients:The Mechanism Of Arterial Smooth Muscle BK_Ca Channels

Objective: To investigate changes of vasomotor function and effect of tetramethylpyrazine?TMP?on the vascular tone of endothelium-denuded human placental arteries from preeclampsia patients.To explore the possible mechanisms of BK_Ca channels in arterial smooth muscle cells underlying these processes and to provide the experimental basis for preeclampsia clinical treatment of TMP.Methods:Using isolated endothelium-denuded human placental arterial rings tone experiment to record vasomotor effects of KCl?80mM?,thromboxane A2 analogue U46619(10^-1010^-7M),TMP(10^-610^-2M)and IbTX?100²00nM?-a specific inhibitor of large conductance calcium-activated potassium channels(BK_Ca).The changes in tone were recorded with Powerlab and DMT system.Comparison the differences of vasomotor of normal pregnancy?NP?group,preeclampsia?PE?group and IbTX-pretreatment group.Results:?1?The contractile response of KCl?80mM?or U46619(10^-7M)induced to PE was significantly higher than NP?p<0.01?;?2?KCl?80mM?induced the plateau tone,and then recovered to the baseline tone,and the relaxation time in the PE wassignificantly longer than that in the NP?p<0.01?;?3?U46619(10^-1010^-7M)induced vasoconstrictions-dependent concentration of placental arterial rings in both groups,while the vasoconstriction in PE group was significant stronger than that in NP group?p<0.05?;?4?IbTX?100nM?had no effect on basic tone of placental arterial rings?p>0.05?;?5?IbTX?100nM?could enhance the U46619-induced vasoconstriction of placental arterial rings increase,which was more significant in PE group?p<0.05?.The U46619-induced vasoconstriction capacity of IbTX+NP group was similar to PE group.There was no significant difference between NP+IbTX group's and PE group's maximum contraction percentage?Emax?and sensitivity of tissue to U46619?pD2??p>0.05?;?6?TMP(10^-210^-6M)induced vasodilatations-dependent concentration of U46619(10^-7M)-preconstriction placental arterial rings in both groups,while the vasodilatation in PE group was significant weaker than that in NP group?p<0.05?;?7?IbTX?100nM?was significantly inhibited vasodilatation capacity of TMP in NP group?p <0.05?,but not inhibit the capacity in NP group?p> 0.05?.The TMP-induced vasodilatation capacity of the two IbTX groups was similar to PE group.The three groups' maximum relaxation percentages?Emax?were similar,but the sensitivity of tissue to TMP?p D2?of IbTX groups was lower than PE group?p<0.05?;?8?IbTX?200n M?had a slight contraction effecton significant diastolic placental arterial rings,but there is no significant difference between the IbTX contraction percentages of PE group and NP group?p>0.05?;?9?TMP had no effect on the basal tone of some vascular rings in PE group?N=10,n=6?and NP group?N=12,n=7??P > 0.05?,while some vascular rings occur an abnormal and reversible vasoconstriction to TMP 10^-3M in PE group?N=10,n=4?and NP group?N=12,n=5?,there is no significant difference between the contraction percentages of PE group and NP group?p>0.05?,the contraction time of PE group was shorter than NP group?p<0.05?.Conclusion:?1?The enhanced vasoconstriction response and decreased vasodilatory capacity of PE may mainly due to the decreasing of BK_Ca channels function in arterial smooth muscle cells;?2?IbTX?100nM?had no effect on basic tone of human placental arteries;?3?TMP could produce remarkable vasodilatation in a concentration-dependent manner on U46619pre-contracted human placental arteries,and this vasodilatation may be concerned with the direct activation of TMP on BK_Ca channels in arterial smooth muscle cells;?4?The declination of vasodilatation capacity of human placental arteries to TMP(10^-610^-2M)in patients with preeclampsia,which may mainly due to the decreasing of BK_Ca channels function in arterial smooth muscle cells;?5?Ib TX?100nM?could significantly inhibit the vasodilatation of human placental arteries to TMP in delivery women with normal pregnancy,but had no inhibition effect onpreeclampsia group;?6?The basic tone of human placental arteries may not be affected by TMP,may also occur an abnormal and reversible vasoconstriction to TMP 10^-3M.