CONTROL OF CAPILLARY PERFUSION IN AGING

该项目的长期目标是确定衰老如何影响血液流向循环的微循环交换血管的分布。衰老的一个不利后果是毛细血管的血液供应减少，毛细血管是人体最小的血管。通过毛细血管输送血液不足的后果包括组织氧气供应不足，特别是在运动期间，以及容易发生心脏病发作和中风等涉及血液流动暂时限制(缺血)的事件。老年人血液循环不良的部分原因可以归因于动脉粥样硬化导致的大动脉斑块形成。然而，我们的实验室最近发现了与毛细血管输送血液相关的关键点。首先，幼年动物(大鼠)的毛细血管灌流似乎涉及到毛细血管后小静脉(供血毛细血管)和毛细血管前小动脉(供血毛细血管)之间的交通。其次，这种交流似乎随着年龄的增长而显著减弱。第三，间质肥大细胞似乎限制了毛细血管后小静脉增强毛细血管血流的能力。我们的具体目标是1)确定幼年大鼠毛细血管灌流的局部决定因素，2)确定毛细血管灌流的静脉控制的年龄依赖性，以及3)确定肥大细胞衍生产物是否导致老年大鼠毛细血管灌流不足。我们要检验的中心假设是，毛细血管血流的控制包括参与动-静脉通讯的血管扩张剂和肥大细胞产生的血管收缩药之间的平衡；此外，这些机制之间的失衡导致了衰老过程中毛细血管血流的减少。

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.