EFFECT OF ACUTE SYSTEMIC HYPOXIA ON VASCULAR-PERMEABILITY AND LEUKOCYTE ADHERENCE IN THE ANESTHETIZED RAT

Objective: The aim was to investigate the effect of acute systemic hypoxia on vascular permeability to macromolecules and on leucocyte adherence to vascular endothelium in vivo. Methods: Experiments were performed on anaesthetised rats with either the intestinal mesentery or the spinotrapezius muscle prepared for in vivo microscopy. To quantify changes in vascular permability, fluorescein isothiocyanate conjugated with serum albumin (FITC-albumin) was given intravenously and the microcirculation was viewed using a mercury source for 30 s periods during air breathing; or before, during, and after breathing 6% O2 for 3 or 20 min. On each occasion the number of FITC leakage sites was counted. In separate experiments acridine orange was given to stain leucocytes and the microcirculation was viewed using a mercury source during air breathing and during a 3 min period of systemic hypoxia. The number of leucocytes that adhered to venular walls for >30 s was counted. Using mesentery, the effects were tested of BW755C, a lipoxygenase inhibitor, and of SM9064, a LTB4 receptor antagonist, upon the increase in leucocyte adherence observed during hypoxia. Results: In rats that breathed air throughout, the number of leakage sites for FITC-albumin in both the spinotrapezius and mesentery remained constant. Moreover, in rats that breathed 6% O2 for 3 or 20 min, the number of leakage sites was not changed in either mesentery or spinotrapezius by hypoxia, but was substantially increased in both preparations by topical application of histamine. However, the number of leucocytes that adhered to the inside of venular walls was significantly increased in both mesentery and spinotrapezius by a 3 min inhalation 6% O2 from 2.83(SEM 0.56) to 4.66(1.77) per 100 mum length of venule and from 2.44(0.33) to 3.35(0.49) respectively during the first period of hypoxia. Between periods of hypoxia the number of adherent leucocytes returned to control in both preparations. Leucocyte adherence was not affected by BW755C (50 or 500 mug.ml-1 applied topically or 10 mg.kg-1 intravenously) or by SM9064 (3 mg-kg-1 intravenously). Conclusions: Acute systemic hypoxia does not affect the vascular permeability to albumin. However, 3 min periods of systemic hypoxia induce significant, but reversible, increases in leucocyte adherence in both muscle and mesenteric venules which in mesentery, at least, is not mediated by LTB4 or other products of the lipoxygenase pathway.