The overall goal of this project is to understand the local processes contributing to tissue oxygen delivery, with particular focus on determining the role of microvascular architecture in controlling flow distribution and hence oxygen delivery in the microvasculature of striated muscle. The proposal arises directly from our previous work which shows that capillary recruitment is achieved by recruitment of groups (networks) of capillaries, and that this recruitment is controlled by an identifiable arteriolar group. We now propose to explore the function of these capillary networks in terms of their exchange capacity for oxygen, and to explore the mechanisms contributing to differential responses in their controlling arterioles. We will test two new hypotheses. (1) All capillary networks (where a capillary network is the capillary group that constitutes the fundamental unit of capillary recruitment) are funtionally equivalent in that they have the same exchange capacity. That is, they have characteristic mass transfer parameters that are not different between networks which are different when compared by single indices such as size, vessel segment density, inflow, cell content etc. (2) Regulatory responses and hemodynamic characteristics in arterioles controlling flow into capillary networks are systematically different in a manner relatable to their sequential location along a single parent vessel. It is further hypothesized that contributions to these local, position-dependent responses are made by differences in adrenergic responses, by flow, and by endothelial function. Studies to evaluate these hypotheses will be undertaken in cremaster muscles of anesthetized Golden hamsters. Hypothesis 1 will be tested by describing capillary network exchange capacity in terms of four mass transfer parameters, and evaluating the constancy of these parameters (1) in networks arising from different arterioles; (2) in different tissue regions; (3) during remodeling associated with tissue growth, or (4) associated with chronically increased blood flow; and (5) arising from """"""""open"""""""" or """"""""closed"""""""" controlling arterioles. Hypothesis 2 will be tested (1) by comparing arteriolar responses (diameter, flow, wall shear stress) to adrenergic agonists and antagonists and to changed 02 concentration in arterioles arising in sequence from the same parent vessel; (2) by using concentration-response curves to compare adrenergic sensitivity in proximally-versus distally-located arterioles from the same sequential group; (3) by comparing responses of these vessels during controlled flow changes either through the whole arteriolar group or locally-produced in single arterioles; and (4) during application of NG-monomethyl-L-arginine or indomethacin to modify endothelial cell function. This study will contribute substantially to understanding local control of blood flow and tissue oxygenation. In particular, by focussing on the role of microvascular architecture, it will facilitate interpretation of the processes underlying adaptive changes, both acute and chronic, e.g. during exercise, adaptation to altered environments (cold, altitude), or pathophysiological changes associated with, for example, chronic anemia, diabetes mellitus or hypertension.
Showing the most recent 10 out of 21 publications
