High pulsatile load ex vivo decreases arterial stiffness by altering the viscous, but not elastic, mechanical properties of the arterial wall

Type of funding sources: Foundation. Main funding source(s): Research Foundation - Flanders (Brussels, BE):

==> [DUTCH]: "Fonds voor Wetenschappelijk Onderzoek (FWO) - Vlaanderen"

The pulsatile character of blood flow in the central arteries results in a local transmission of energy to the arterial wall, acting on both the viscous and elastic components of the arterial wall. The amplitude of the "pulsatile load" is known to modulate the mechanosensitive properties of blood vessels.

To evaluate the behavior of both the viscous and elastic components of the mouse aorta under altered pulsatile loading. Moreover, we aimed to assess regional differences in (arterial) tissue stiffness, as well as the contribution of vascular smooth muscle cell (VSMC) contractility under altered pulsatile conditions.

Aortic segments from C57Bl6 (n=9) mice were mounted in a Rodent Oscillatory Set-up for Arterial Compliance (ROTSAC), and subjected to high frequency (10 Hz) cyclic stretch at alternating loads (i.e. 20 to 100 mmHg with mean pressures ranging from 80 to 200 mmHg). Diastolic and systolic diameter, compliance, and the Peterson elastic modulus (Ep), as a measure of aortic stiffness, were determined. Viscous modulus (EV) was extracted from pressure-diameter tracings by eliminating loop hysteresis. Afterwards, the elastic modulus (EE) was calculated as the slope of the resulting pressure-diameter tracing:

(P_elastic)= (P_total) - (EV * (dD/dt))

To assess regional differences in response to changes in pulsatile load, the most proximal aortic region (i.e., thoracic ascending aorta) was compared to a more distal aortic region (i.e., abdominal infrarenal aorta).

Increasing pulse pressure from 40 to 100 mmHg decreased arterial stiffness (298 ± 9 vs. 270 ± 9 mmHg; p < 0.0001). Analyzing viscoelasticity revealed that increasing pulsatile load from 40 to 100 mmHg decreased EV (0.24 ± 0.02 vs. 0.21 ± 0.02 mmHg.s/mm; p < 0.01) but not EE. 50 mM KCl-induced VSMC contraction increased vessel stiffness (298 ± 9 mmHg vs. 395 ± 12 mmHg; p < 0.0001). This effect was pronounced at low pulse pressures (20 and 40 mmHg) while at higher pulse pressures (60, 80 and 100 mmHg) contraction-induced stiffness did not occur. Interestingly, the distal region of the aorta was stiffer than the proximal region (367 ± 60 vs. 289 ± 36 mmHg; p < 0.01) and had a higher EV (0.77 ± 0.2 vs. 0.21 ± 0.05 mmHg.s/mm; p < 0.0001). Increasing pulsatile load from 40 to 100 mmHg decreased the EV from distal aortic tissue more than the EV of tissue from the proximal region (-0.26 ± 0.02 vs. -0.06 ± 0.007 mmHg.s/mm).

High pulsatile load decreased arterial stiffness by decreasing the viscous mechanical properties. This effect was more pronounced in the distal region of the aorta.