An electrophysiological study of microvascular permeability and its modulation by chemical mediators.

In continuous microvessels the permeability barrier is constituted by the endothelium, consisting of a single layer of endothelial cells separated by hydrophilic clefts. Ions and small hydrophilic solutes permeate the endothelium via the intercellular spaces, and the dimensions of this pathway determine the permeability. Endothelial permeability characteristics have been extensively studied by physiological techniques used on whole organs. It is known that permeability of venules increases after stimulation with inflammatory mediators, probably by a mechanism involving formation of widenings of the interendothelial cleft, termed leaks. To the present knowledge about the function of the microvascular endothelium my studies have added the following information: 1. The electrical resistance or conductance of endothelium recorded on single frog microvessels in vivo vary by at least three orders of magnitude from the tight brain endothelium (Rm = 1870 omega cm2, Gm = 0.53 mScm-2) to the microvascular endothelia of skin (Rm = 24-70 omega cm2, Gm = 14-42 mScm-2), muscle (Rm = 23-36 omega cm2, Gm = 28-43 mScm-2) and mesentery (Rm = 1-3 omega cm2, Gm = 0.33-1.0 Scm-2). 2. Potassium ion permeabilities calculated from the electrical conductances average 8.5 x 10(-7), 3.4 x 10(-5), 5.7 x 10(-5), and 80 x 10(-5) cm sec-1 for brain, skin, muscle and mesenteric microvessels, respectively. These values comply with what has been predicted from whole-organ experiments. 3. Venules are 1.5-2 x more permeable to ions than arterioles. 4. Ion permeabilities of capillaries are not much different from those of venules, and since the surface area of venules is comparable to that of capillaries, venules may be important exchange vessels for small solutes. 5. The specific electrical resistance of frog blood-brain barrier is similar to that of a tight epithelium, resembling brain endothelium by several criteria. 6. The electrical resistance of brain endothelium is at least one order of magnitude smaller than that of the endothelial cell membrane, strongly indicating that microvascular permeability to small solutes is mainly paracellular in brain, as it is in other organs. 7. Ion permeability of frog blood-brain barrier is reversibly increased by various autacoids: serotonin, bradykinin, ATP, ADP, AMP, og LTC4. These receptor-agonists all induce similar changes: permeability increases within 1-2 sec after administration, rapidly peaks with values less than two-fold the control value and reverses at a much slower rate (5-15 min).(ABSTRACT TRUNCATED AT 400 WORDS)