Work

Breeding Characteristics and Dose-dependent Blood Pressure Responses of Transgenic Cyp1a1–Ren2 Rats

Year: 2018

Type: article

Abstract: 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.

Source: Comparative Medicine

DOI: 10.30802/aalas-cm-17-18000026

Authors: Catherine J Leader, Barbara J Clark, Amber R Hannah, Ivan A Sammut, Gerard T Wilkins, Robert J Walker

Institution: University of Otago

Language: English

Topic: Blood Pressure and Hypertension Studies

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: American Society of Nephrology, Australian and New Zealand Society of Nephrology, Maurice and Phyllis Paykel Trust, Otago Medical Research Foundation