Modulation of arteriolar blood flow by inhibitors of arachidonic acid oxidation after thermal injury: Possible role for a novel class of vasodilator metabolites

K. G. Proctor, S. Shatkin, P. M. Kaminski, J. R. Falck, J. H. Capdevila

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

To examine the contribution of arachidonic acid (AA) metabolites to the maintenance of cutaneous vasomotor tone after thermal injury, enzyme inhibitors were topically applied to the hamster cheek pouch before and after a spot burn. By use of video microscopy, blood flow was measured in adjacent arterioles that supplied the injured site. Ringer's solutions containing no drug (vehicle), indomethacin (cyclooxygenase inhibitor), BW755c (cyclooxygenase/lipoxygenase inhibitor), or ketoconazole (lipoxygenase/cytochrome P450 inhibitor) continuously suffused the entire tissue. There were no effects of these drugs on preburn blood flow at concentrations that blocked the vascular effects evoked by topical AA. In all groups, blood flow transiently increased after burn and thereafter decreased to levels that were altered by treatment. These results could not be attributed to alterations in vascular reactivity becuase neither the burn nor the drugs altered the vasodilation evoked by adenosine or prostacyclin. Relative to Ringer's, indomethacin had no effect, BW755c caused vasodilation, and ketoconazole caused vasoconstriction, which suggests that cytochrome P450 products might be vasoactive mediators in injured tissue. Therefore, purified synthetic compounds were compared with known vasodilators. The potency was prostacyclin > 12R-hydroxyeicostetraenoic acid > adenosine = 5,6 epoxyeicosatrienoic acid > AA, which supports the hypothesis that AA can be the source of a novel class of nonprostaglandin vasodilator compounds. In addition, at least one of the vasodilator responses was stereospecific. Nevertheless, the exact explanation for the differential effects of AA inhibitors on postburn blood flow is unknown.

Original languageEnglish (US)
Pages (from-to)1185-1196
Number of pages12
JournalCirculation
Volume77
Issue number5
DOIs
StatePublished - 1988
Externally publishedYes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Modulation of arteriolar blood flow by inhibitors of arachidonic acid oxidation after thermal injury: Possible role for a novel class of vasodilator metabolites'. Together they form a unique fingerprint.

Cite this