CONTROL OF CAPILLARY PERFUSION IN AGING

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The long-term objective of this project is to determine how aging affects the distribution of blood flow to the microcirculatory exchange vessels of the circulation. An adverse consequence of aging is a decreased supply of blood to the capillaries, the smallest blood vessels in the body. Consequences of insufficient blood delivery through capillaries include inadequate oxygen supply to tissue, especially during exercise, and a predisposition to episodes such as heart attacks and strokes that involve a temporary restriction of blood flow (ischemia). Poor circulation in the elderly can be partially attributed to plaque formation in large arteries as a result of atherosclerosis. However, our lab has recently exposed key points relevant to blood delivery through capillaries. First, capillary perfusion in young animals (rats) appears to involve communication between postcapillary venules (which drain the capillaries) and precapillary arterioles (which feed the capillaries). Second, this communication appears to be significantly attenuated with aging. Third, interstitial mast cells appear to limit the ability of postcapillary venules to enhance capillary perfusion. Our specific aims are to 1) identify local determinants of capillary perfusion in young rats, 2) determine the age-dependency of venular control of capillary perfusion, and 3) determine whether mast cell-derived products contribute to deficient capillary perfusion in old rats. Our central hypothesis to be tested is that control of capillary perfusion includes a balance between vasodilators involved in arteriovenular communication and vasoconstrictors produced by mast cells; furthermore, an imbalance between these mechanisms contributes to decreased capillary perfusion in aging.