Aims:Autoantibody against the second extracellular loop ofα-adrenoceptor(α-AA) which had been found in hyperte...
Li Yan,Xiu-Li Cheng,Fan Ding,Yun-Hui Du,Hui-Rong Liu,Ji-Min Cao 1 Department of Physiology and Pathophysiology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences,School of Basic Medicine,Peking Union Medical College,Beijing 100005,P.R.China
Background:Growing evidence indicates that primary or secondary activation of immune mechanisms have been impl...
Zhong-Hua DAI~1,Li YAN~1,Guang-Zhao YANG~2,Su-Li ZHANG~2,Hui-Rong LIU~(2,3),Ji-Min CAO ~1 1 Department of Physiology and Pathophysiology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences,School of Basic Medicine,Peking Union Medical College,Beijing 100005,China
Autoimmune activities have been implicated in the pathogenesis of hypertension.High levels of autoantibodies against the second extracellular loop of α1-adrenoceptor(α1-AR autoantibody,α1-AA) are found in patients with hypertension,and α1-AA could exert a α1-AR agonist-like vasoconstrictive effect.However,whether the vasoconstrictive effect of α1-AA is enhanced in hypertension is unknown.Using aortic rings of spontaneously hypertensive rats(SHR) and normotensive Wistar-Kyoto(WKY) rats,we observed the vasoconstrictive responses to α1-AA with phenylephrine(α1-AR agonist) as a positive control drug.Aortic nitrotyrosine levels were also measured by ELISA and immunohistochemistry.The results showed that the aortic constrictive responses to α1-AA and phenylephrine(both 1 nmol L-1-10 μmol L-1) were greater in SHR than in WKY rats.Endothelial denudation or L-NAME(a non-selective NOS inhibitor)(100 μmol L-1) increased α1-AA- or phenylephrine-induced vasoconstrictions both in SHR and WKY.However,selective iNOS inhibitor 1400W(10 μmol L-1) enhanced the α1-AA-induced aortic constriction in WKY,but not in SHR.The aortic nitrotyrosine level was significantly higher in SHR than WKY,as shown by both ELISA and immunohistochemistry.These results indicate that the vasoconstrictive response to α1-AA is enhanced in SHR,and this altered responsiveness is due to endothelial dysfunction and decreased NO bioavailability.The study suggests an important role of α1-AR autoimmunity in the pathogenesis and management of hypertension especially in those harboring high α1-AA levels.
YAN LiTAN XiaoQiuCHEN WenXuanZHU HongCAO JiMinLIU HuiRong
Objective Primary or secondary activation of immune mechanisms has been implicated in the pathogenesis of hype...
Li YAN~1,Yun-hui DU~2,Zhong-mei HE~3,Hui-rong LIU~(2,3),Ji-min CAO~1 (1.Department of Physiology and Pathophysiology,Institute of Basic Medical Sciences Chinese Academy of Medical Sciences,School of Basic Medical Sciences Peking Union Medical College,Beijing 100005,China
