| AIM and background Previous research by our group has found that endothelin-type A(ET_A)receptors and endothelin-type B(ET_B)receptors in rat coronary artery smooth muscle cells(VSMCs)can be up-regulated by weakly oxidized low-densitylipoprotein(mmLDL)through in vitro organ culture.To investigate whether mmLDL affects the quantity and activity of ET_A receptors and ET_B receptors in mouse mesenteric artery by activating the p38 mitogen-activated protein kinase(MAPK)inflammatory pathway.Previous research by our group has found that ET_A receptors and ET_B receptors in rat coronary artery smooth muscle cells(VSMCs)can be up-regulated by mmLDL through in vitro organ culture.METHODS mmLDL was injected into the tail vein of mice,and p38 MAPK inhibitor SB 203580 was administered intraperitoneally.Mesenteric artery ring segments vasoconstriction dose-response curves affected by Sarafotoxin 6c(S6c)and endothelin-1(ET-1)was recorded by the myography system.The mRNA levels of ET_B receptor,ET_A receptor and IL-6 were detected by real-time polymerase chain reaction(RT-PCR),The protein expression of ET_B receptor,ET_A receptor,IL-6,p38 MAPK,p-p38 MAPK,NF-?B and p-NF-?B were detected by Western blot;The serum concentration of IL-6 were detected by ELISA kit.RESULTS The contractile response of S6c and ET-1 to blood vessel segments was significantly increased by mmLDL(P<0.001).The expression of ET_A receptor,ET_B receptor,and IL-6 protein levels were significantly increased(P<0.01).The expression of p-p38 MAPK and p-NF-?B protein levels were significantly increased(P<0.01).The expression of IL-6 in serum was significantly increased(P<0.001).These effects of mmLDL can be decreased by p38 MAPK inhibitor SB 203580.CONCLUSION mmLDL up-regulates the expression of ET_A and ET_B receptors in mouse mesenteric artery,and increases the mediated vasoconstriction function,which is related to the activation of p38 MAPK inflammatory pathway and downstream NF-?B pathway. |
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