Reddy H K, Campbell S E, Janicki J S, Zhou G, Weber K T
Department of Internal Medicine, University of Missouri-Columbia 65212.
J Lab Clin Med. 1993 Mar;121(3):510-21.
Vascular permeability of the coronary and mesenteric circulation is increased in association with the arterial hypertension that accompanies either endogenous activation of the renin-angiotensin-aldosterone system (RAAS) or exogenous administration of angiotensin II (AII). Whether this occurs as a result of increased intravascular pressure or of elevations in plasma concentrations of AII or aldosterone (ALDO) (or both) is unclear. This acute study of filtration-independent coronary fluid exchange and macromolecular permeability was undertaken to address these issues in open-chest, anesthetized dogs. The influence of arterial hypertension, with or without associated elevations in plasma AII or ALDO (or both), on coronary permeability was examined by monitoring the response in cardiac lymph flow, protein concentration, and capillary and intramural coronary artery structure. Experimental groups received a 90-minute intravenous infusion of either AII (n = 8), methoxamine (MX; n = 7), or ALDO plus MX (n = 5) in equipotent doses that raised arterial pressure to comparable levels. When we compared these animals with normotensive, instrumented controls (n = 5), we found that (1) lymph flow was a function of arterial and microvascular pressures in each group; (2) increased protein permeability, myocardial edema, extravasated red cells, and infused colloidal carbon were found in both ventricles with AII, together with endothelial discontinuities and enhanced abluminal capillary endothelial vesicle formation, when plasma ALDO had risen significantly in response to AII; and (3) macromolecular permeability was no different from that in controls after MX or ALDO plus MX. Based on this short-term study of acute arterial hypertension, we would conclude that acute elevations in microvascular pressure increase fluid flux, whereas increased circulating effector hormones of the RAAS, not plasma ALDO or hypertension alone, alter coronary microvascular structure and permeability to macromolecules Responsible mechanisms remain to be defined.
在伴随肾素-血管紧张素-醛固酮系统（RAAS）内源性激活或外源性给予血管紧张素II（AII）的动脉高血压情况下，冠状动脉和肠系膜循环的血管通透性会增加。目前尚不清楚这是由于血管内压力升高，还是AII或醛固酮（ALDO）血浆浓度升高（或两者兼有）所致。本急性研究旨在通过对开胸麻醉犬进行与滤过无关的冠状动脉液体交换和大分子通透性研究，以解决这些问题。通过监测心脏淋巴流量、蛋白质浓度以及冠状动脉毛细血管和壁内结构的反应，研究了伴有或不伴有血浆AII或ALDO（或两者）升高的动脉高血压对冠状动脉通透性的影响。实验组接受90分钟的静脉输注，分别给予AII（n = 8）、甲氧明（MX；n = 7）或ALDO加MX（n = 5），剂量等效，均可使动脉压升高至相当水平。当我们将这些动物与正常血压、植入仪器的对照组（n = 5）进行比较时，发现：（1）每组淋巴流量均是动脉压和微血管压的函数；（2）在AII组中，两个心室均出现蛋白质通透性增加、心肌水肿、红细胞外渗和注入的胶体碳，同时伴有内皮细胞连续性中断和管腔外毛细血管内皮小泡形成增加，此时血浆ALDO因AII而显著升高；（3）MX组或ALDO加MX组的大分子通透性与对照组无差异。基于对急性动脉高血压的短期研究，我们得出结论：微血管压力的急性升高会增加液体通量，而RAAS循环效应激素增加，而非单独的血浆ALDO或高血压，会改变冠状动脉微血管结构和对大分子的通透性。其具体机制仍有待确定。
