Leader Catherine J, Clark Barbara J, Hannah Amber R, Sammut Ivan A, Wilkins Gerard T, Walker Robert J
Department of Medicine, University of Otago, Dunedin, New Zealand.
Hercus-Taieri Resource Unit, University of Otago, Dunedin, New Zealand.
Comp Med. 2018 Oct 1;68(5):360-366. doi: 10.30802/AALAS-CM-17-18000026. Epub 2018 Sep 5.
Hypertension is a leading risk factor for cardiovascular and chronic kidney disease. A new rodent model (transgenic male Cyp1a1-Ren2 rats) provides reversible induction of hypertension through the addition of indole-3-carbinol (I3C) to the diet, without the need for surgical intervention, thus giving researchers control over both the onset of hypertension and its magnitude (I3C dose-dependency). We here report the breeding performance and productivity of Cyp1a1-Ren2 rats. Despite being transgenic, these animals proved to be efficient breeders. In addition to confirming inducible and reversible dose-dependent hypertension (by using I3C doses of 0.125%, 0.167%, and 0.25% [w/w] in the diet for 14 d, followed by normal chow for 4 d), we demonstrated that hypertension can be sustained chronically (14 wk) by continuous dosing with I3C (0.167% [w/w]) in the diet. In chronically dosed male rats, systolic blood pressure continued to rise, from 173 ± 11 mm Hg after 1 mo to 196 ± 19 mm Hg after 3 mo, with no adverse phenotypic features observed. In conclusion, Cyp1a1-Ren2 rats are a useful animal model to investigate hypertension-induced end-organ damage and potential new therapeutic targets to manage hypertension.
高血压是心血管疾病和慢性肾病的主要危险因素。一种新的啮齿动物模型（转基因雄性Cyp1a1-Ren2大鼠）通过在饮食中添加吲哚-3-甲醇（I3C）可实现高血压的可逆诱导，无需手术干预，从而使研究人员能够控制高血压的发作及其严重程度（I3C剂量依赖性）。我们在此报告Cyp1a1-Ren2大鼠的繁殖性能和生产力。尽管是转基因动物，但这些动物被证明是高效的繁殖者。除了确认可诱导和可逆的剂量依赖性高血压（通过在饮食中使用0.125%、0.167%和0.25%[w/w]的I3C剂量14天，然后正常喂食4天）外，我们还证明通过在饮食中持续给予I3C（0.167%[w/w]）可使高血压长期维持（14周）。在长期给药的雄性大鼠中，收缩压持续升高，从1个月后的173±11毫米汞柱升至3个月后的196±19毫米汞柱，未观察到不良表型特征。总之，Cyp1a1-Ren2大鼠是一种用于研究高血压诱导的终末器官损伤以及管理高血压潜在新治疗靶点的有用动物模型。
