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Long-term control of vascular functions, including tissue perfusion and peripheral resistance, is achieved by continuous structural adaptation of vessels in response to mechanical and metabolic stimuli. We used a quantitative theoretical model to analyze how the integrated action of structural responses in each segment of a microvascular network can lead to stable, realistic distributions of vessel diameter and wall thickness throughout the network. The input data for the model was obtained from two networks in the rat mesentery, supplying areas of 27 and 54 mm2, containing 546 and 913 vessel segments, and with overall blood flow rates of 402 and 1113 nl/min. The topological arrangement of segments and the length, diameter, blood flow velocity and hematocrit of each segment were measured during intravital microscopy. A previously described hemodynamic simulation was used to predict the distributions of blood flow, hematocrit and oxygen. In the adaptation model, diameter and wall mass of each segment were assumed to vary in response to fluid shear stress, circumferential wall stress, and tissue metabolic status, as indicated by local partial pressure of oxygen. Metabolic signals were assumed to be propagated upstream and downstream along vascular segments. The following features were found to be essential: increased wall shear stress and increased metabolic signal stimulate increases in diameter; increased circumferential stress stimulates increase in wall mass; the circumferential stress-derived stimulus decreases with increasing wall thickness. Predicted relationships in vascular networks between pressure and shear stress and between circumferential wall shear stress and vessel diameter in arterioles and venules were then consistent with experimental observations. The results of the present model show that long-term regulation of both vessel diameter and wall thickness in terminal vascular beds can be explained by vascular reactions to hemodynamic and metabolic stimuli with uniform response characteristics, in the sense that the equations and parameters representing structural changes in diameter and wall thickness resulting from a given set of stimuli are identical for every segment in the network. Also, the model can be used to analyze consequences of changes in vascular adaptation characteristics related, for example, to changes in endothelial autacoid production or expression of ion channels by changing the corresponding reaction parameters.
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J. Vasc. Biol. 42, Sup:2 (2005) pp57-58