Maturation is associated with changes in rat cerebral artery structure, biomechanical properties and tone

Abstract

This study evaluated the hypothesis that physiological maturation affects cerebral artery smooth muscle-endothelial interactions involved in pressure-induced tone and alters the dimensional and biomechanical properties of small posterior cerebral arteries (PCA). Secondary branches of PCA from young (4-5 weeks old, n=11), adult (14-16 weeks old, n=11) and mature (44-47 weeks old, n=11) male Sprague-Dawley rats were isolated, cannulated, pressurized and subjected to a range of intraluminal pressures (10-110 mmHg) to determine tone with and without pharmacologic nitric oxide synthase (NOS) inhibition. Measurements of passive lumen diameter and wall thickness as a function of pressure were used to determine changes in structure, distensibility and wall stress; histological analysis was performed on vessel cross-sections to assess collagen and elastin contents. Although pressure-dependent tone decreased significantly during ageing, differences between groups were abolished by NOS inhibition. Vessel diameters increased in adult vs. young rats (at 90 mmHg, 233 ± 6.0 μm vs. 192 ± 4.5 μm; P<0.05), possibly secondary to somatic growth. Further ageing was associated with reductions in lumen diameter (207 ± 6.5 μm; P<0.05), increased wall and media thickness (and wall/lumen ratio) and cross-sectional area. Distensibility and wall collagen were unchanged, although elastin content was significantly reduced. Maturation is associated with differences in PCA dimensional properties that indicate a pattern of initial outward eutrophic, followed by inward hypertrophic remodelling. Functionally, the contribution of basal NO increases with age in a way that reduces pressure-dependent tone and diminishes vasodilator reserve.