The role of NO-cGMP pathway inhibition in vascular endothelial-dependent smooth muscle relaxation disorder of AT1-AA positive rats: protective effects of adiponectin.

摘要: Abstract Angiotensin II type 1 receptor autoantibodies (AT1-AA) cause endothelial-dependent smooth muscle relaxation disorder. It is well understood that impairment of the NO–cGMP signaling pathway one mechanisms However, it still unclear whether AT1-AA induces disorder via pathway. In addition, adiponectin exerts vascular endothelial protection through Therefore, purpose this investigation was to assess mechanism induced by and role in attenuating dysregulation. Serum endothelin-1 (ET-1), were detected enzyme-linked immunosorbent assay. preeclamptic patients, there an increased level AT1-AA, which positively correlated with ET-1 negatively adiponectin, as elevated levels suggested injury. AT1-AA-positive animal models actively immunized second extracellular loop angiotensin (AT1R-ECII) for eight weeks. thoracic aortas positive rats, elevated, endothelium-dependent vasodilation decreased. Paradoxically, upstream element NO-cGMP pathway, NO production not decreased but increased, ratio p-VASP/VASP, established biochemical endpoint reduced. Moreover, nitrotyrosine gp91phox indicate presence peroxynitrite (ONOO-) superoxide anion (O2·−) increased. Pretreatment ONOO- scavenger FeTMPyP or O2·−scavenger Tempol normalized vasorelaxation. Key enzymes responsible synthesis also assessed. iNOS protein expression p-eNOS(Ser1177)/eNOS Preincubation inhibitor 1400 W eNOS agonist nebivolol restored Further experiments showed p-AMPKα (Thr172)/AMPKα, controls activity, have been Furthermore, component AMPK, reduced sera rats supplementation significantly contents, improved vasodilation, production, inhibited gp91phox, overexpression, phosphorylation at Ser1177 aorta rats. These results may aggravate enhancing This discovery shed a novel light on clinical treatment diseases associated AT1-AA.