G. Öjteg

Oxygen radicals in postischaemic damages in the kidney.

SummaryOxygen radicals in postischaemic damages in the kidney: M. Wolgast, A. Bayati, O. Hellberg, Ö. Källskog, K. Nygren and G. Öjteg, Inst. of Physiology and Medical Biophysics, University of Uppsala, Sweden; Ischemic acute renal failure is characterized by a severe depression of the glomerular filtration rate (GFR), isosthenuria and deficient potassium secretion, whereas the total renal blood flow may remain largely intact. As to these symptoms, it would seem established that the depression of GFR results from an ischaemia-induced augmented aging and hence rejection of tubular cells, which thence blocks the tubular lumen. As expected this blockade can be prevented by osmotic diuretics. The isosthenuria and the deficient potassium excretion, on the other hand, results probably from a medullary ischaemia, the latter due to the action by oxygen-derived free radicals in the sense the subsequent damage to the capillary membrane leads to a massive extravasation of plasma and consequent intracapillary trapping of red cells. In line with this idea, superoxide-dismutase (SOD) or Allopurinol may ameliorate these changes. In the recovery phase of postischaemic renal failure, the most prominent feature is the blocking of the ascending loop of Henle with Tamm/Horsfall-protein which, if not washed-out during the first week, leads to a complete degeneration of the nephron. Unfortunately, the process would seem to be unaffected by treatment with e.g. osmotic diuretics and SOD or Allopurinol.

The net electric charge of proteins. A comparison of determinations by Donnan potential measurements and by gel electrophoresis

We compare a new method for the determination of the net charge of proteins based on Donnan potential measurements, as described briefly by Ojteg, G., Nygren, K. and Wolgast, M. (1987) Acta Physiol. Scand. 129, 277-286, with a conventional method using polyacrylamide gel electrophoresis. The new technique utilizes the Donnan potential, which develops over a semipermeable membrane that separates the non-permeating protein from the surrounding bath of the same ionic composition as the protein solution, to determine the net valency. The advantages of this method, besides its simplicity, are that it can determine the charge of, e.g., a protein in a free-fluid phase and that the pH and ionic composition of the bathing fluid can be varied over a broad range. The Donnan potential decreased to half its original value when the ionic strength was doubled. Usually a protein concentration of 1-10 mg.ml-1 must be used. The Donnan potential method was applied to determine the net charges of a series of proteins with different isoelectric points. The values showed close agreement with the data obtained by gel electrophoresis.

On the Intrinsic Control of Capillary Permeability

The permeability of the renal capillary membranes is suggested to be controlled not only by external forces, but also by the prevailing Starling pressures, in the sense that a large net driving force is followed by a large hydraulic resistance, and vice versa. This means that, in spite of variations of the net driving force, the fluid transfer may remain fairly constant—in other words an autoregulation of the membrane permeability is suggested. The need for such a mechanism would seem obvious, i.e., since otherwise even small changes in glomerular filtration and/or peritubular capillary uptake might lead to drastic changes in the urinary output. The hypothesis has its basis in a new model, in which it is supposed that a flexible gel/fiber-matrix, rather than a rigid porous membrane, constitutes the membrane. The size, shape, and permeability characteristics of such a membrane will be the result of the balance between, on the one hand, the above mentioned physical forces and, on the other, the mechanics of the gel/fiber structure. Here, the tension of the fibers acts to restrict expansion, whereas membrane-fixed negative charges, via the resulting electroosmotic pressure and balancing hydrostatic pressure, act to resist compression. Regarding the intra-membranous net driving force, the hydrostatic pressure gradient valid in the Starling model will be replaced by an electroosmotic net driving force, i.e., where the magnitude and direction of the force is governed by the electric field. A gel/fiber-matrix membrane can furthermore be predicted to possess a self-rinsing ability, a feature typical of, e.g., the glomerular capillary membrane. Regarding external control of the membrane permeability, all factors which affect the isoelectric point of the structure carrying the charges can be predicted to govern the membrane characteristics.