Heart rate and blood pressure in male Ts65Dn mice: a model to investigate cardiovascular responses in Down syndrome.

Down syndrome (Ds) is the most common chromosomal cause of intellectual disability that results from triplication of chromosome 21 genes. Lower blood pressure (BP) and heart rate (HR) in response to exercise and other stressors are prevalent in Ds, and are mediated by autonomic dysfunction. The Ts65Dn mouse is a model of Ds that is commonly used in preclinical studies, but has not been formally investigated for cardiovascular responses in conscious mice. Based on human studies of Ds, we hypothesized Ts65Dn would have lower BP and HR, but similar arterial stiffness. BP was quantified in conscious wild-type (WT) and Ts65Dn. A main effect for strain was observed for all BP measures (systolic, diastolic, mean, pulse pressure), with WT higher than Ts65Dn. Pulse wave velocity was similar between WT and Ts65Dn. High-frequency power spectra was higher in WT suggesting autonomic differences between strains. Freely moving HR was higher in WT versus Ts65Dn in both the dark and light cycles, although a main effect of circadian cycle was also present (dark> light). Similar to what is observed in humans, Ts65Dn has a lower BP which may be attributed to autonomic differences and result in preservation of arterial function with advancing age. Ts65Dn thus appears to capture the Ds cardiovascular phenotype across the lifespan. These data support further use of Ts65Dn to investigate mechanisms that may lead to altered BP and HR responses in Ds.