Heart Rate and Blood Pressure in Ts65Dn and Wild‐type Mice

Abstract

Down syndrome (Ds), resulting from triplication of the 21st chromosome, is the most common chromosomal abnormality. Severity can vary between individuals, but Ds is commonly associated with developmental delays and cognitive impairments. Ds also presents with lower resting blood pressure, which is often viewed as a beneficial health trait. However, the blood pressure response during exercise is attenuated compared to the general population. An inability to appropriately regulate blood pressure likely influences daily living in Ds. Hence, investigating cardiovascular abnormalities is important for identifying intervention targets in this population. We aimed to document conscious heart rate and blood pressure of Ts65Dn (Ts) mice, a model of Ds, and hypothesized that Ts mice would have lower resting blood pressure and heart rate, but normal arterial stiffness compared to their wild‐type (WT) counterparts. Mice were tested for systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) using a CODA volume‐pressure tail cuff system (Kent Scientific, Torrington, CT) at six (n=14/group), nine (n=7/group) and twelve (n=8 WT, n=6 Ts) months of age. Arterial stiffness was measured for a subset of nine‐month‐old mice (n=4/group) using pulse wave velocity (PWV) calculated as distance/time (cm/msec) and normalized to MAP (mmHg). Freely‐moving heart rate (HR) for twelve‐month‐old animals (n=11 WT, n=6 Ts) during the light and dark periods of circadian cycle were quantified with a MouseOx pulse oximetry and heart rate neck collar (Starr Life Sciences, Oakmont, PA). Data shown are presented as WT vs. Ts, mean±SD. WT mice had higher SBP (108±19 vs. 82±13 mmHg, p=0.01), DBP (82±18 vs. 59±12 mmHg, p=0.02) and MAP (91±18 vs. 67±12 mmHg, p=0.01) compared to Ts counterparts at nine months of age. Similar data were collected at six and twelve months, where SBP, DBP and MAP were all higher in WT mice (p<0.05). Absolute (198.1±18.2 vs. 152.3±56.0 cm/msec, p=0.17) and normalized (2.0±0.4 vs. 2.3±0.6 cm/msec/mmHg, p=0.41) PWV was not significantly different between WT and Ts groups. This is comparable to Ds, where differences in PWV disappear when normalized to their lower blood pressure. While HR was not different during the light (resting) cycle between WT and Ts mice (673±83 vs. 661±30 bpm, p=0.79), WT mice had higher HR during the dark (active) cycle (759±40 vs. 710±41 bpm, p=0.03). The lower HR in Ts during more active periods is similar to Ds, suggesting a reduced ability to increase cardiac output during times of activity. Thus, Ts65Dn mice showcase blood pressure and heart rate characteristics that recapitulate the cardiovascular profile observed in Ds individuals. Ts65Dn is a model that can uncover more information about the progression and etiology of blood pressure and heart rate regulation across the lifespan in Ds. Future directions include exploration of the autonomic contributions to these present findings.Support or Funding InformationFunded by 1 R15 HD076379‐01A1, CNR supported by 1 R15 HD076379‐01A1S1.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.