AJP - Heart and Circulatory Physiology, Vol 249, Issue 1 14-H19, Copyright © 1985 by American Physiological Society
Endothelium-dependent vasodilation by melittin: are lipoxygenase products involved?
U. Forstermann and B. Neufang
Vascular relaxation in response to acetylcholine and other vasodilator
compounds has been shown to depend on intact endothelial cells. These
dilator compounds obviously induce the formation of an unstable
endothelium-derived relaxing factor or factors (EDRF) from the intima which
relax the subjacent smooth muscle cells. The chemical identity of this
factor (these factors) is still unclear. In the present study we
demonstrate that endothelium-dependent relaxation of rabbit aorta was
induced by melittin, a polypeptide toxin that activates phospholipase A2 to
liberate polyunsaturated fatty acids (especially arachidonic acid) from
membrane phospholipids. The relaxation induced by melittin had several
properties similar to the acetylcholine relaxation. It was inhibited by
potential inhibitors of phospholipase (mepacrine and
p-bromophenacylbromide), by inhibitors of lipoxygenase
(nordi-hydroguaiaretic acid, compound BW 755C, and
5,8,11,14-eicosatetraynoic acid) but not by the cyclooxygenase inhibitor
indomethacin. An exogenous preparation of phospholipase C also induced
endothelium-dependent relaxations. These findings support the hypothesis
that oxidized metabolites of polyunsaturated fatty acids (e.g., arachidonic
acid) may be involved directly (as mediators) or indirectly in the process
of endothelium-dependent relaxation. On the other hand, exogenous
arachidonic acid was a comparatively weak endothelium-dependent relaxant.
However, this does not exclude an important role of endogenous arachidonic
acid since the exogenous acid may not sufficiently reach its site of
metabolism.
