Project: Research project

Project Details


A new pathway of arachidonic acid metabolism has recently been
discovered. Although the metabolites from that pathway could be
present in almost all cells, the biological actions are largely
unknown. Our studies with several structurally dissimilar
inhibitors have implicated a role for these substances, the
epoxyeicosatrienoic acids (EETs), in the peripheral circulation in
physiologic and pathological conditions. To test for a potential
role for the EETs in the regulation of tissue blood flow, we
propose to characterize the effects of purified synthetic EETs on
microvascular hemodynamics, granulocyte/endothelial
interactions, and microvascular permeability. These effects will
be directly observed with in vivo microscopy and also quantitated
with histologic evaluation of fixed, stained tissue specimens. The
mechanisms of these effects will be explored by
pharmacologically altering the activity of adenylate or gyanylate
cyclase in vivo. This information would be integrated with our
continued investigation of the effects of various inhibitors on the
burn-induced acute inflammatory response in the hamster cheek
pouch and on the fat-induced absorptive hyperemia response in
the rat intestine. Because EET formation seems to be favored in
these conditions, we propose to compare EET concentrations in
biological fluids with changes in the microcirculatory variables.
Overall, the proposed research could lead to the development of
innovative new therapies for the treatment of acute
inflammation. Furthermore, these results could reveal the
existence of fundamentally new mechanisms of tissue blood flow
Effective start/end date12/31/8911/30/92


  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute


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