Key result
High-fat diet increases Ang II-induced thoracic aortic contraction ~3-fold in insulin-resistant rats.
Why the study?
The study aimed to understand and compare vascular reactivity to angiotensin II and receptor expression in thoracic and abdominal aorta under insulin resistance.
Insulin resistance induces segmental differences in Angiotensin II vascular reactivity and receptor expression between the thoracic and abdominal aorta in rats, which may contribute to the heterogeneity of aneurysm incidence.
Answers are grounded in this paper and cite their sources.
No practice change from rat data; leaves open whether insulin resistance drives human aneurysm heterogeneity via segmental reactivity.
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: Con: 319 ± 29 and HFD: 1095 ± 72, P < 0.001) and unaltered (Emax in mg/mm: 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.
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Karpe et al. (2011) studied Insulin resistance (n=12). High fat diet (insulin resistance) vs. Control diet was evaluated on Ang II-induced contractile responses in thoracic aorta (Emax in mg/mm) (p=<0.001). High fat diet-induced insulin resistance significantly increased Ang II-induced contractile responses in the thoracic aorta (1095 vs 319 mg/mm, P<0.001) but not the abdominal aorta.
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