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减少了对毛细血管的血液供应，毛细血管是体内最小的血管。 通过毛细血管输送的血液不足的后果包括组织供氧不足，特别是在运动期间，以及易患心脏病发作和中风等涉及血流暂时受限（缺血）的事件。 老年人的血液循环不良部分归因于动脉粥样硬化导致的大动脉斑块形成。然而，我们的实验室最近暴露了与通过毛细血管输送血液相关的关键点。 第一，年轻动物（大鼠）的毛细血管灌注似乎涉及毛细血管后小静脉（为毛细血管引流）和毛细血管前小动脉（为毛细血管供血）之间的交流。 其次，这种沟通似乎随着年龄的增长而明显减弱。 第三，间质肥大细胞似乎限制了毛细血管后微静脉增强毛细血管灌注的能力。我们的具体目标是：1）确定年轻大鼠毛细血管灌注的局部决定因素，2）确定毛细血管灌注的微静脉控制的年龄依赖性，3）确定肥大细胞衍生的产物是否有助于老年大鼠毛细血管灌注不足。 我们要检验的中心假设是，毛细血管灌注的控制包括参与动静脉通信的血管舒张剂和肥大细胞产生的血管收缩剂之间的平衡;此外，这些机制之间的不平衡有助于衰老中毛细血管灌注的减少。

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.