Development of a new device to study ex-vivo the arterial stiffness of isolated aortic segments of a mouse with dysfunctional endothelium in the large arteries

In clinical practice there is a large amount of blood-pressure(BP) lowering drugs available, but, unfortunately, they rarely succeed to reduce long-term CV risk completely. Moreover, it was found that patients with high BP, who respond poorly to their treatment, are those with a stiffer aorta. Indeed, stiffening of the large arteries (e.g. the aorta) also increases CV risk and indicates that treating arterial stiffening in addition to hypertension may result in a better outcome. This was also suggested in the most recent guidelines of the European Society of Cardiology. Little is known about the mechanisms that cause arterial stiffening. Most studies on arterial compliance and stiffness of isolated mouse elastic arteries are done with the isometric myograph: arterial segments are gradually stretched and wall stress is determined revealing stress-strain relationships. The experiments are, however, done under static, isometric conditions, whereas pacing experiments performed in rodents and humans showed that arterial compliance is strongly frequency-dependent. Therefore, we needed an ex-vivo technique to study arterial compliance and stiffness of segments subjected to cyclic stretch. The Rodent Oscillatory Tension Set-up to study Arterial Compliance (ROTSAC) is an in-house developed device to assess arterial stiffness parameters and active isotonic properties of periodically stretched isolated mouse aortic segments. It is, to our knowledge, the first ex-vivo set-up that exposes the isolated mouse aorta to cyclic stretch at physiological frequencies (600/min) and amplitudes (60-200 mm Hg). We successfully acquired pressure diameter (PD) loops at physiological pressure and frequency with high reproducibility in healthy C57Bl6 mouse aorta. In the present project, we test the new ROTSAC set-up in mouse models of endothelial (dys)function to announce it as a valuable ex-vivo technique to measure arterial stiffness. Therefore, several mouse models with varying eNOS (endothelial NO synthase, the enzyme that releases the dilating factor NO) activity and degree of arterial stiffness are used.

Keywords:ANTIHYPERTENSION, NITRIC OXIDE SYNTHESIS, MOUSE MODELS, KNOCK OUT MOUSE

Disciplines:Animal biology, General biology, Biophysics, Cardiac and vascular medicine, Physiology, Veterinary medicine