Angiotensin II (AngII), a major effector of the renin-angiotensin system, exerts critical roles in regulating vascular function. AngII infusion induces abdominal aortic aneurysms (AAAs) and exacerbates atherosclerosis in hypercholesterolemic mice. We determined the effects of AngII infusion on endogenous AngII regulation and AngII-mediated AAAs and atherosclerosis. AngII infusion increased renal, but not plasma, AngII concentrations in male mice. AngI concentrations were decreased modestly in kidney, but more profoundly in plasma, during AngII infusion. Bovine AngII (DRVYVHPF) has one amino acid difference from mouse AngII (DRVYIHPF) that can be distinguished by LC-MS/MS to determine exogenous versus endogenous peptides. AngII infusion reduced endogenous renal AngII concentrations. To determine whether the residual endogenous AngII exerted an effect on exogenous AngII-mediated AAAs and atherosclerosis, aliskiren (a direct renin inhibitor) was administered to AngII-infused male LDL receptor deficient mice. Although aliskiren did not attenuate AAAs in AngII-infused mice, atherosclerotic lesion size was reduced. In conclusion, endogenous AngII concentrations are reduced during AngII infusion but still contribute to atherosclerosis, but not AAA, in AngII-infused hypercholesterolemic mice.

中文翻译：

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内源性血管紧张素Ⅱ对输注血管紧张素Ⅱ的小鼠腹主动脉瘤和动脉粥样硬化的影响

血管紧张素II（AngII）是肾素-血管紧张素系统的主要效应物，在调节血管功能中起关键作用。AngII输注会诱发高胆固醇血症小鼠的腹主动脉瘤（AAAs），并加剧动脉粥样硬化。我们确定了AngII输注对内源性AngII调节和AngII介导的AAA和动脉粥样硬化的影响。AngII输注可增加雄性小鼠的肾脏AngII浓度，但不会增加血浆AngII浓度。AngII输注期间，肾脏中的AngI浓度适度降低，但血浆中的AngI浓度降低更深。牛AngII（DRVYVHPF）与小鼠AngII（DRVYIHPF）有一个氨基酸差异，可通过LC-MS / MS进行区分，以确定外源肽与内源肽。AngII输注降低了内源性肾脏AngII浓度。为了确定残留的内源性AngII是否对外源性AngII介导的AAA和动脉粥样硬化产生影响，向注入AngII的雄性LDL受体缺陷型小鼠施用aliskiren（直接肾素抑制剂）。尽管阿利吉仑在注入AngII的小鼠中不会减弱AAA，但是动脉粥样硬化病变的大小却减小了。总之，在AngII输注的高胆固醇血症小鼠中，在AngII输注期间内源性AngII浓度降低，但仍有助于动脉粥样硬化，但不助长AAA。