Renal capillary permeability and intravascular red cell aggregation after ischaemia. I. Effects of xanthine oxidase...

The macromolecular permeability of renal capillaries and the intravascular red cell aggregation resulting from 45 min of warm ischaemia were investigated. The effects of the xanthine oxidase inhibitor Allopurinol on these factors and also on the post-ischaemic nephron function were also studied. Following ischaemia there was a more than 10-fold increase in the transport from plasma to renal hilar lymph both of plasma proteins and of two isomers of lactate dehydrogenase (LDH)-the nearly neutral LDH-M4 and the negatively charged LDH-H4. The ischaemia also resulted in massive intravascular red cell aggregation, especially in the renal medulla. Through reduction of plasma xanthine oxidase activity from 13.1 +/- 1.1 microU microliter-1 (mean +/- SEM) to essentially zero by Allopurinol, the capillary leakiness was substantially diminished with almost complete normalization after 120 min. At the same time the relative volume of trapped red cells was reduced; in the inner stripe of the outer medulla, for example, it decreased from 11.3 +/- 1.7% in untreated animals to 4.0 +/- 1.1% after treatment with 20 mg of Allopurinol given intravenously 3 h before the ischaemia. Oral feeding with 4 mg of Allopurinol day-1 for one week gave essentially the same result. The net driving force for filtration after treatment with this drug was thus 19 mmHg, as against 26 mmHg in the normal kidney and the resulting SNGFR was half the normal. The total filtration rate was proportionally more reduced to less than 1/3 of the normal. Tubular obstruction was still present but was not as severe as in untreated kidneys (Karlberg et al., 1982b) where the tubular fluid flow and thereby the filtration are essentially zero. It is suggested that oxygen free radicals increased the macromolecular permeability and the adhesiveness of white blood cells and that these two factors combined underlie the aggregation of red blood cells in the medullary vasa recta with consequent persistence of medullary ischaemia.