447Small artery structure and function during ageing in the sheep

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Abstract

Purpose

Cardiovascular disease increases exponentially with age and is a major cause of mortality in the elderly. Age related changes in the structure and function of large and small arteries result in a less compliant vasculature that is less able to respond to vasodilator signals. In large conduit arteries remodelling of the extracellular matrix leads to increased stiffness of the artery wall. However, the changes that occur in small arteries are less clear. In this study we have investigated the effects of ageing on the structure and function of small arteries in an ovine model of ageing.

Methods

Mesenteric small arteries (~400 μ internal diameter) from six young ( < 18 months) and four old ( > 8 years) sheep were mounted in a pressure myograph. Responses to the vasoconstrictor noradrenaline (0.1-100 μM) and the vasodilator acetylcholine(0.01-100 μM) were recorded. Arteries were then deactivated by incubation in calcium free physiological salt solution containing 2mM EGTA and the passive changes in lumen diameter and wall thickness recorded in response to increasing pressure 5-180mmHg. From these data wall cross sectional area, media/lumen ratio and wall stress and strain were calculated and plotted to obtain the stress/strain relationship, which is an indicator of distensibility independent of artery geometry. Collagen and elastin content of artery sections were measured with Picrosirius red and Millers stains respectively.

Results

There was an increase in lumen diameter, media thickness and medial cross sectional area in the old compared to the young showing outward hypertrophic remodeling of the small arteries with ageing. The media/lumen ratio was decreased and the stress/strain relationship was shifted to the right in old compared to young arteries, suggesting increased distensibility with ageing. There was increased collagen and elastin in the medial layer of arteries from old sheep compared to young. There was no change in the response to noradrenaline or acetylcholine with ageing.

Conclusion

Collectively these data show structural and mechanical remodelling of small mesenteric arteries without changes in their contractile or dilator responsiveness. This suggests that remodelling of small arteries during ageing leads to compensatory changes that act to normalise the strain on the artery wall.

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