R. Mian et Jm. Marshall, EFFECT OF ACUTE SYSTEMIC HYPOXIA ON VASCULAR-PERMEABILITY AND LEUKOCYTE ADHERENCE IN THE ANESTHETIZED RAT, Cardiovascular Research, 27(8), 1993, pp. 1531-1537
Objective: The aim was to investigate the effect of acute systemic hyp
oxia on vascular permeability to macromolecules and on leucocyte adher
ence to vascular endothelium in vivo. Methods: Experiments were perfor
med on anaesthetised rats with either the intestinal mesentery or the
spinotrapezius muscle prepared for in vivo microscopy. To quantify cha
nges in vascular permability, fluorescein isothiocyanate conjugated wi
th serum albumin (FITC-albumin) was given intravenously and the microc
irculation was viewed using a mercury source for 30 s periods during a
ir 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. I
n separate experiments acridine orange was given to stain leucocytes a
nd the microcirculation was viewed using a mercury source during air b
reathing 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 leuc
ocyte adherence observed during hypoxia. Results: In rats that breathe
d 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 insi
de 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 hy
poxia the number of adherent leucocytes returned to control in both pr
eparations. 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 o
f systemic hypoxia induce significant, but reversible, increases in le
ucocyte adherence in both muscle and mesenteric venules which in mesen
tery, at least, is not mediated by LTB4 or other products of the lipox
ygenase pathway.