Abstract TAC198: Hypertensive heart disease phenotype in male and female Schlager mice

Hypertensive heart disease (HHD) is the second most common cause of heart failure with a global prevalence of around 33%. Hypertensive heart disease (HHD) involves structural and functional changes of the left ventricle, the left atrium and intramural coronary arteries due to persistent hypertension. Genetically hypertensive Schlager (BPH/2J) mice are a known model of high blood pressure with high sympathetic nerve activity. In this work we wanted to identify if Schlager mice can be a potential model to study hypertensive heart disease. Both male and female adults (4-months; 4M) and middle aged (10 months; 10M) BPH/2J and their controls (BPN/3J) mice were used. Mean arterial pressure (MAP) was measured using the non-invasive blood pressure measurement system. The MAP was significantly higher in adult male BPH/2J mice (158±26 mmHg) compared to the BPN/3J controls (117±9 mmHg). In case of adult females, MAP was higher in BPH/2J mice (129±10 mmHg) compared to BPN/3J mice (105±14 mmHg). We found hypertension induced structural changes in the heart of adult and middle-aged male and female Schlager mice. However, we found no change in pleural effusion, collagen content, and fibrotic marker- atrial natriuretic peptide expression irrespective of the strain, sex and age of the mice. Echocardiography data in male hypertensive mice revealed a reduced ejection fraction (BPH/2J: 41±4% vs. BPN/3J: 61±8%) and fractional shortening (BPH/3J: 20±3% vs. BPN/3J: 32±6%) irrespective of the age of the mice. In contrast, female hypertensive mice echocardiography revealed preserved ejection fraction (BPH/2J: 55±11% vs. BPN/3J: 62±8%) and fractional shortening (BPH/3J: 29±7% vs. BPN/3J: 33±6%). In conclusion, our work suggests that hypertensive BPH/2J mice can be used as a model to study the impact of high blood pressure, stress, and age on heart failure progression.