Sex based cardiovascular differences in adult and middle-aged hypertensive schlager mice

Hypertension can lead to hypertensive heart disease (HHD). Genetically hypertensive Schlager (BPH/2J) mice are valuable models for hypertension research. However, comprehensive sex- and age-related differences in cardiovascular phenotype and HHD progression in this model are currently lacking. Here, we aimed to investigate age- and sex-related changes in blood pressure and cardiac parameters in hypertensive BPH/2J mice and normotensive BPN/3J controls. We utilized adult (4-months) and middle-aged (10-months) mice and non-invasively assessed their blood pressure using a tail cuff method and cardiac parameters through echocardiography. Elevated mean arterial pressure (mmHg ± SD) was observed in both male (BPH/2J: 158 ± 26 versus BPN/3J: 117 ± 9) and female mice (BPH/2J:129 ± 10 versus BPN/3J: 105 ± 14) compared to their normotensive counterparts, starting at adulthood, and persisting through middle-age. Echocardiographic analysis revealed significant cardiac dysfunction in adult hypertensive males, including reductions in ejection fraction (%±SD) (BPH/2J: 41 ± 4 versus BPN/3J: 61 ± 8), and fractional shortening (%±SD) (BPH/2J: 20 ± 3 versus BPN/3J: 32 ± 6), indicating the progression of HHD. In contrast, hypertensive females showed preserved cardiac function despite elevated blood pressure, suggesting sex-based differences in how chronic hypertension affects cardiac health. There was no cardiac fibrosis or pleural effusion in either hypertensive or normotensive mice, regardless of age and sex. In conclusion, this study highlights the BPH/2J mouse as an important model for investigating sex-based cardiovascular differences in the context of hypertension.