Insulin resistance induces a segmental difference in thoracic and abdominal aorta: Differential expression of AT1 and AT2 receptors

Abstract

Objectives: The study was pursued to understand and compare the vascular reactivity to angiotensin II (Ang II) and its receptor expression in thoracic and abdominal aorta under insulin resistance. Methods: Vascular reactivity to Ang II was recorded isometrically, AT1/AT2 receptor gene and protein expression was checked by RT-PCR and western blotting, respectively, and abundance of phospho (serine-10 Ph) H3 on promoter regions of Agtr1/Agtr2 genes was done by chromatin immunoprecipitation assay in aortic rings isolated from high fat diet (HFD)-fed rats. Results: Our functional studies showed an increased (Emax in mg/mm 2: Con: 319 ? 29 and HFD: 1095 ? 72, P < 0.001) and unaltered (E max in mg/mm 2: Con: 299 ? 29 and HFD: 350 ? 20, mean ? SEM, n = 6) Ang II-induced contractile responses in thoracic and abdominal aorta of HFD rats, respectively, as compared to control rats. Interestingly, AT2R-mediated relaxation was increased in abdominal aorta (% relaxation: Con: 25 ? 5.3 and HFD: 76.4 ? 8.9, P < 0.001) of HFD rats but not in thoracic aorta (% relaxation: Con: 25 ? 5.2 and HFD: 32 ? 5.2, mean ? SEM, n = 6). At the molecular level, increased mRNA (?14-folds) and protein expression (?2.5-folds) of AT2R in abdominal aorta of HFD rats was found as compared to control rats. However, AT1R mRNA and protein expression did not show any change. Chromatin immunoprecipitation with phospho H3 showed increased abundance of ser-10 phosphorylation on Agtr1 and Agtr2 gene promoter regions in thoracic and abdominal segments, respectively. But it got decreased on Agtr2 and Agtr1 genes promoter regions in thoracic and abdominal segments, respectively. Conclusion: We provide first evidence that insulin resistance induces segmental difference in thoracic and abdominal aorta and this may provide reason of heterogeneity for incidence of aneurysms. ? 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.