Plante G E, Chakir M, Ettaouil K, Lehoux S, Sirois P
Department of Medicine, Université de Sherbrooke, Canada.
Can J Physiol Pharmacol. 1996 Jul;74(7):824-33. doi: 10.1139/cjpp-74-7-824.
In this review paper, three aspects related to alteration in capillary permeability, based on a series of recent observations from this laboratory, are examined. Firstly, the determinants of capillary extravasation, which include pre- and post-capillary resistances in different microcirculation networks, as well as endothelial permeability per se, are described with particular reference to the heterogeneous character of both regulatory components, reported by this and other groups. Secondly, the endothelium-interstitium relationship, responsible in part for the maintenance of the interstitial compartment physicochemical characteristics, is introduced as an important factor in regulating the traffic of vital nutrients delivered to the cell mass, and the removal of waste products from the cellular compartment to the microcirculation, for ultimate excretion. Examined in this manner, it appears that modulation of capillary permeability is essential for the maintenance of cellular life, yet the neurohumoral mechanisms involved in the control of microcirculation networks are just starting to be identified. A number of morbid conditions characterized by multiorgan involvement exhibit a common pathophysiological denominator which involves endothelium-interstitium relationships, as illustrated in experimental animal models of arterial hypertension, diabetes mellitus, heart failure, and degenerative renal diseases. Enhanced capillary permeability associated with local interstitial edema in specific organs, such as the heart and the kidney, in arterial hypertension and diabetes mellitus, as well as decreased permeability in peripheral tissues, such as the skeletal muscle and the skin, in congenital cardiomyopathy, have been documented. It is likely that alteration in the characteristics of interstitial matrix composition contributes to target organ damage in these examples of systemic disorders from different etiologies. Thirdly, the recent identification of autocoids and hormones involved in the direct and indirect control of capillary permeability has led to the development of pharmacological tools capable of modulating pre- and post-capillary vascular tonus, as well as endothelial permeability. Angiotensin II antagonism, bradykinin B1-receptor inhibition, and modulation of eicosanoid production, in particular thromboxane A2, are associated in some of the above-described disorders, with normalization of capillary permeability defects, and occasionally with improvement in organ function. The eventual development of agents capable of directly controlling the physicochemical characteristics of the interstitial matrix should be of interest, not only for preventing the development of irreversible matrix structural alterations but also for facilitating the traffic of metabolites between capillaries and the cell mass of vital organs.
在这篇综述论文中，基于本实验室最近的一系列观察结果，对与毛细血管通透性改变相关的三个方面进行了研究。首先，描述了毛细血管外渗的决定因素，包括不同微循环网络中的毛细血管前和后阻力，以及内皮通透性本身，并特别提及了本研究小组和其他小组报道的这两种调节成分的异质性。其次，介绍了内皮-间质关系，它部分负责维持间质隔室的物理化学特性，是调节输送到细胞团的重要营养物质的运输以及将细胞隔室中的废物清除到微循环以最终排泄的重要因素。以这种方式进行研究后发现，毛细血管通透性的调节对于维持细胞生命至关重要，但参与微循环网络控制的神经体液机制才刚刚开始被确定。一些以多器官受累为特征的病态情况表现出一种共同的病理生理特征，涉及内皮-间质关系，如在动脉高血压、糖尿病、心力衰竭和退行性肾脏疾病的实验动物模型中所示。在动脉高血压和糖尿病中，与特定器官（如心脏和肾脏）局部间质水肿相关的毛细血管通透性增强，以及在先天性心肌病中，外周组织（如骨骼肌和皮肤）的通透性降低，都已得到证实。在这些不同病因的系统性疾病实例中，间质基质成分特征的改变可能导致靶器官损伤。第三，最近对参与直接和间接控制毛细血管通透性的自分泌物质和激素的鉴定，导致了能够调节毛细血管前和后血管张力以及内皮通透性的药理学工具的开发。在上述一些疾病中，血管紧张素II拮抗、缓激肽B1受体抑制以及类花生酸生成的调节，特别是血栓素A2的调节，与毛细血管通透性缺陷的正常化相关，偶尔还与器官功能的改善相关。能够直接控制间质基质物理化学特性的药物的最终开发应该是有意义的，这不仅有助于防止不可逆的基质结构改变的发展，还能促进毛细血管与重要器官的细胞团之间代谢物的运输。
