Physiology · May 2026
Blood Pressure and Cardiac Function are Age and Sex Dependent in a Mouse Model of Down Syndrome
By Vasileva A, Buckman MA, Kalra H et al.
Adults with Down syndrome (DS) are at an increased risk for cardiovascular disease, and understanding the progression of these risks from youth to older age is essential. The Ts65Dn mouse model recapitulates many features of DS, but cardiovascular function has not been longitudinally evaluated in this model. This study aimed to characterize age-related changes in blood pressure, left-ventricular performance, and baroreflex function in female and male Ts65Dn mice at 3, 6, 12, and 22 months of age. We measured conscious blood pressure, and cardiac catheterization provided measurements of left ventricular function. The baroreflex was quantified from changes in heart rate and blood pressure evoked using the modified Oxford technique. Blood pressure declined with age in Ts65Dn and was lower in male mice, which is consistent with previous findings in humans. Interestingly, female mice exhibited higher blood pressure at 3 and 6 months, but this pattern reversed by 12 months. In the presence of lower stroke volume, cardiac output was preserved by increased heart rate in young mice and increased contractility in old mice. Ts65Dn mice exhibited impaired autonomic regulation across the lifespan. 3-month-old mice had the lowest pulse pressure interval, and 22-month-olds the highest. Baroreflex analysis showed age-related changes in minimum heart rate (P1) and a shift in the setpoint (P4/BP50) to the left in older mice. Overall, aging in mice showed a distinct blood pressure pattern with previously unrecognized sex differences, increased contractility, preserved ejection fraction, and a baroreflex shifted to lower pressures. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.