YI 2.2 Spontaneous Cardiovascular Ageing of C57BL6 Mice Results in the Development of Aortic Stiffness Prior to Periphral Blood Pressure Alterations

Abstract

Background

Although generally assumed to be an adaptive response to increased blood pressure (BP), arterial stiffness is now recognized as an independent predictor of cardiovascular (CV) events [1]. Moreover it precedes hypertension in at least two mouse models [2,3]. Therefore, the present study aims to investigate the temporal development of aortic stiffening and peripheral blood pressure (BP) alterations in spontaneously ageing mice.

Methods

A longitudinal cardiovascular characterization of spontaneously ageing C57Bl6 mice (2, 4, 6, 9, 12 and 24- month old) (male, n > 8) was performed. This includes in vivo analysis of peripheral BP (Coda) and aortic pulse wave velocity (aPWV, Vevo2100), combined with ex vivo aortic studies of isometric reactivity (organ baths) and aortic stiffness measurements (Peterson modulus, Ep) in the Rodent Oscillatory Tension set-up for Arterial Compliance (ROTSAC).

Results

In vivo and ex vivo characterisation confirms that aortic stiffness precedes peripheral BP alterations in spontaneously ageing C57Bl6 mice, with significantly increased aPWV from 6 month of age (Figure A), whereas peripheral BP measurement only shows elevated pulse pressure in 24 month old mice (30% increase vs. all other ages, Figure B). Ex vivo investigation of the thoracic aorta further reveals that the aortic stiffening is both contraction-independent (Figure C) and dependent (Figure D), since older mice display increased contractions to phenylephrine (PE) (Figure E and F).

Conclusion

Spontaneously ageing C57Bl6 mice present with significant aortic stiffness by 6-months of age, which is both contraction-dependent and independent in origin. Aortic stiffness thereby precedes the development of peripheral BP alterations by 18 months.