Arterial Wall Structure Function Relations

Changes in the structure and function of the aorta and to a lesser extent the central arteries are the principal features underlying changes in PP. Large 'elastic arteries' are composed of three layers: the intima, the tunica media, and the adventitia [23], In the proximal (thoracic) aorta, elastic lamellae are normally attached to smooth muscle cells to form 'contractile-elastic units' [24] that damp pulsation. Collagen is found in the adventitia and media, while elastin is located in the tunica media, not only in the internal and external elastic laminae, but also throughout the interstitial spaces surrounding the vascular smooth muscle (VSM) cells. Collagen fibers are oriented longitudinally, elastin forms a trabeculated sheath, and VSM are oriented in a spiral pattern. This geometric pattern contributes to the sequence of loading of the arterial wall that generally begins at low pressure with VSM, then shifts at higher pressures to elastin, and finally at the highest pressures to collagen. Overall, this sequence creates a non-linear loading response of arterial diameter and wall tension that limits pressure-dependent arterial dilation. Farther down the arterial tree, the proportion of wall constituents changes substantially. Elastin decreases markedly and the proportion of VSM cells increases. Distal arteries function less as dampers and more as 'conduits'. In resistance arterioles, there is little elastin and a markedly reduced proportion of collagen; the function of these microvessels is highly dependent on the tonic state of contraction of VSM and its relation with the endothelium.

The combined effects of wall thickness (h), wall stiffness (Young's modulus, E) and lumen radius (R) determine the impedance and compliance properties of large arteries. Changes in smooth muscle tone and remodeling in response to alterations in ambient flow can modulate each of the foregoing properties of the artery. The slope of the non-linear relation between arterial wall stress and strain (load) is the elastic modulus (E) of the vessel. The effective elastic modulus at any given distending pressure depends on the composition of the arterial wall (i.e., relative content of the three major structural elements - elastin, collagen and VSM), the state of smooth muscle activation, the extent of cross-linking within and between collagen and elastin fibers and the content and properties of other matrix components including various proteo-glycans. Vascular loading characteristics also vary within the cardiac cycle, with contractile-elastic units being preferentially loaded during diastole, while elastin and collagen are loaded more fully in systole.

Stiffness of a given artery is pressure-dependent and non-linear, and varies according to the stiffness measure evaluated. Measures of arterial stiffness have differing dependencies on the three independent and interdependent determinants (E, h and R) that combine differently in various settings. Clinical estimation of aortic stiffness usually involves measurement of pulse wave velocity (PWV), which determines the speed of wave propagation in an artery, or characteristic impedance (Zc), which determines the early systolic pressure rise associated with a given pulsatile flow prior to the return of any reflected waves. These related measures of arterial function differ considerably in their relation to arterial lumen radius:

where E = elastic modulus, h = arterial thickness, and R = arterial radius.

An increase in smooth muscle tone generally has little effect on PWV because the reduction in R (which reduces wall tension) is counteracted by the increases in medial thickness (h) and the intrinsic increase in E caused by VSM contraction. In contrast, Zc invariably increases substantially with local VSM activation because of the amplified (fivefold greater) dependency of Zc on R. Any process that primarily increases effective arterial wall stiffness (Eh) will limit the increase in R at a given distending pressure and will therefore have a greater effect on Zc than PWV.

Each artery has a range of maximum compliance (or minimum Zc) that usually corresponds to the physiologic operating range of pressures occurring in that vessel [25]. Relative to this nominal value, physiologic systems (e.g. sympathetic nervous and renin-angiotensin or local nitric oxide generative) that control vascular tone have relatively complex effects on local and systemic vascular elastic properties as described above. The in vivo regional response to in creased VSM tone is further complicated by the associated changes in MAP. A localized increase in smooth muscle tone will tend to increase Zc as noted above. However, when MAP increases because of associated changes in resistance vessel tone, large artery diameter and Zc may remain unchanged (or may increase) while PWV is likely to be increased because of the attenuated dependency of PWV on R. Thus, PWV is also more dependent on diastolic BP than is Zc.

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