On perfusion through isolated lungs from male Sprague-Dawley rats,
equinatoxin caused a dose-dependent increase in the wet to dry weight ratio. Ratios were significantly elevated above control values at
equinatoxin concentrations of 80-200 ng/ml. The increased ratios were accompanied by an increase in the permeability of the lung vasculature. When
equinatoxin was perfused through isolated lungs at concentrations of 100 ng/ml or greater, significantly more [3H]
polyethylene glycol (PEG; approximately 900 mol. wt) was retained in the extravascular space as compared to controls. Perfusion pressures of the lung were significantly elevated above controls at
equinatoxin concentrations greater than 100 ng/ml. These effects of
equinatoxin were not mediated by degranulation of mast cells, as preperfusion of the lung with 100 or 200 microM Na
cromolyn or 1 microM
lanthanum chloride did not modify the pulmonary response to
equinatoxin. At concentrations of
equinatoxin below 150 ng/ml the fluid movement appears to be restricted primarily to intracellular, or possibly interstitial, spaces, as no significant amounts of [3H]
polyethylene glycol were recovered by tracheal lavage. At concentrations of
equinatoxin equal to or greater than 150 ng/ml, significant amounts of PEG were washed from the trachea. As it is a potent inducer of
pulmonary edema,
equinatoxin may become an important probe to study fluid regulation in the lung.