alpha-Toxin perfusion: a new method for selective impairment of endothelial function in isolated vessels or intact...

We describe a method for selectively permeabilizing endothelial cells, using the membrane pore forming exoprotein Staphylococcus aureus alpha-toxin. Experiments were performed in rabbit central ear artery or its main side branch under isometric conditions, on the isolated perfused kidney, or in cannulated pressurized renal arteries. In presence of alpha-toxin, endothelial-dependent vasodilator responses elicited by acetylcholine or A23187 were abolished, whereas the sensitivity of smooth muscle cells to constrictors (norepinephrine, phenylephrine, or KCl) or dilators (sodium nitroprusside) was not affected. The results indicate that restricting the alpha-toxin to the luminal surface induces selective impairment of vascular endothelial function. This method of eliminating endothelium-dependent vasodilator responses may prove to be useful in the study of endothelial-smooth muscle interactions of isolated small arteries and intact vascular beds.