TY - JOUR
T1 - Modulation of arteriolar blood flow by inhibitors of arachidonic acid oxidation after thermal injury
T2 - Possible role for a novel class of vasodilator metabolites
AU - Proctor, K. G.
AU - Shatkin, S.
AU - Kaminski, P. M.
AU - Falck, J. R.
AU - Capdevila, J. H.
PY - 1988
Y1 - 1988
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0023877945&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023877945&partnerID=8YFLogxK
U2 - 10.1161/01.CIR.77.5.1185
DO - 10.1161/01.CIR.77.5.1185
M3 - Article
C2 - 3129211
AN - SCOPUS:0023877945
SN - 0009-7322
VL - 77
SP - 1185
EP - 1196
JO - Circulation
JF - Circulation
IS - 5
ER -