CONSEQUENCES OF ALTERATION IN CAPILLARY-PERMEABILITY

In this review paper, three aspects related to alteration in capillary permeability, based on a series of recent observations from this labo ratory, are examined. Firstly, the determinants of capillary extravasa tion, which include pre- and post-capillary resistances in different m icrocirculation 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. Sec ondly, the endothelium-interstitium relationship, responsible in part for the maintenance of the interstitial compartment physicochemical ch aracteristics, 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 microcirculati on, for ultimate excretion. Examined in this manner, it appears that m odulation of capillary permeability is essential for the maintenance o f cellular life, yet the neurohumoral mechanisms involved in the contr ol of microcirculation networks are just starting to be identified. A number of morbid conditions characterized by multiorgan involvement ex hibit a common pathophysiological denominator which involves endotheli um-interstitium relationships, as illustrated in experimental animal m odels of arterial hypertension, diabetes mellitus, heart failure, and degenerative renal diseases. Enhanced capillary permeability associate d with local interstitial edema in specific organs, such as the heart and the kidney, in arterial hypertension and diabetes mellitus, as wel l as decreased permeability in peripheral tissues, such as the skeleta l muscle and the skin, in congenital cardiomyopathy, have been documen ted. It is likely that alteration in the characteristics of interstiti al matrix composition contributes to target organ damage in these exam ples of systemic disorders from different etiologies. Thirdly, the rec ent identification of autocoids and hormones involved in the direct an d indirect control of capillary permeability has led to the developmen t of pharmacological tools capable of modulating pre- and post-capilla ry vascular tonus, as well as endothelial permeability. Angiotensin II antagonism, bradykinin B-1-receptor inhibition, and modulation of eic osanoid production, in particular thromboxane A,, are associated in so me of the above-described disorders, with normalization of capillary p ermeability defects, and occasionally with improvement in organ functi on. 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 irreversib le matrix structural alterations but also for facilitating the traffic of metabolites between capillaries and the cell mass of vital organs.