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

Area of Science:

• Cardiovascular Science
• Nephrology
• Animal Models

Background:

• Hypertension is a major risk factor for cardiovascular and chronic kidney diseases.
• Existing models often require surgical intervention, limiting control over hypertension induction and severity.

Purpose of the Study:

• To report the breeding performance and productivity of the novel transgenic male Cyp1a1-Ren2 rat model.
• To validate the inducible, reversible, and dose-dependent nature of hypertension in this model.
• To assess the feasibility of chronic hypertension induction for long-term studies.

Main Methods:

• Utilized indole-3-carbinol (I3C) administration in the diet to induce hypertension in Cyp1a1-Ren2 rats.
• Tested varying I3C doses (0.125%, 0.167%, 0.25%) for 14 days, followed by a washout period.
• Maintained chronic hypertension for 14 weeks using continuous 0.167% I3C diet.

Main Results:

• Cyp1a1-Ren2 rats demonstrated efficient breeding despite being transgenic.
• Inducible and reversible hypertension was confirmed, showing dose-dependency with I3C.
• Sustained hypertension was achieved in chronically dosed rats, with systolic blood pressure rising from 173 ± 11 mm Hg to 196 ± 19 mm Hg over 3 months without adverse effects.

Conclusions:

• Cyp1a1-Ren2 rats are efficient breeders and a viable model for hypertension research.
• This model allows precise control over hypertension onset, magnitude, and duration.
• It serves as a valuable tool for investigating hypertension-induced end-organ damage and therapeutic targets.