title: Antibodies against AT1 receptors are associated with vascular endothelial and smooth muscle function impairment: protective effects of hydroxysafflor yellow A.
abstract: Ample evidence has shown that autoantibodies against AT1 receptors (AT1-AA) are closely associated with human cardiovascular disease. The aim of this study was to investigate mechanisms underlying AT1-AA-induced vascular structural and functional impairments in the formation of hypertension, and explore ways for preventive treatment. We used synthetic peptide corresponding to the sequence of the second extracellular loop of the AT1 receptor (165-191) to immunize rats and establish an active immunization model. Part of the model received preventive therapy by losartan (20 mg/kg/day) and hyroxysafflor yellow A (HSYA) (10 mg/kg/day). The result show that systolic blood pressure (SBP) and heart rate (HR) of immunized rats was significantly higher, and closely correlated with the plasma AT1-Ab titer. The systolic response of thoracic aortic was increased, but diastolic effects were attenuated markedly. Histological observation showed that the thoracic aortic endothelium of the immunized rats became thinner or ruptured, inflammatory cell infiltration, medial smooth muscle cell proliferation and migration, the vascular wall became thicker. There was no significant difference in serum antibody titer between losartan and HSYA groups and the immunized group. The vascular structure and function were reversed, and plasma biochemical parameters were also improved significantly in the two treatment groups. These results suggest that AT1-Ab could induce injury to vascular endothelial cells, and proliferation of smooth muscle cells. These changes were involved in the formation of hypertension. Treatment with AT1 receptor antagonists and anti oxidative therapy could block the pathogenic effect of AT1-Ab on vascular endothelial and smooth muscle cells.
authors.affiliation: Department of Physiology, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Jin
authors.forename: Wenhui
authors.initials: W
authors.lastname: Zhang
authors.forename: Weiran
authors.initials: W
authors.lastname: Chai
authors.forename: Yanqian
authors.initials: Y
authors.lastname: Zheng
authors.forename: Jianming
authors.initials: J
authors.lastname: Zhi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D003971:Diastole / Q000187:drug effects; D016232:Endothelins / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007114:Immunization; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D009200:Myocardial Contraction / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000097:blood; D009599:Nitroprusside / Q000494:pharmacology; D011809:Quinones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D013599:Systole / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000906:Antibodies; D002316:Cardiotonic Agents; D016232:Endothelins; D008077:Lipoproteins, LDL; D011809:Quinones; D044140:Receptor, Angiotensin, Type 1; C099252:oxidized low density lipoprotein; C085278:hydroxysafflor yellow A; D009599:Nitroprusside; D009569:Nitric Oxide; D002599:Chalcone; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin