Role of prostanoids and 20-HETE in mediating oxygen-induced constriction of skeletal muscle resistance arteries

This study determined the contribution of cytochrome P450 (CP450) 4A enzyme metabolites of arachidonic acid in mediating the constriction of isolated rat skeletal muscle resistance arteries in response to elevated PO2 Gracili s arteries (GA) were viewed via television microscopy and constrictor respo nses to elevated PO2 were measured with a video micrometer. Endothelium rem oval and treatment of GA with 17-octadecynoic acid (17-ODYA; suicide substr ate inhibitor of CP450 4A enzymes) impaired oxy gen-induced constriction of the vessels; treatment of endothelium-denuded GA with 17-ODYA eliminated r esponses to elevated PO2 NOS inhibition and inhibition of EET production ha d no effect on oxygen-induced constriction of the vessels, although cycloox ygenase inhibition with indomethacin impaired GA responses to elevated PO2. Treatment of GA with dibromododecenyl methylsulfimide (DDMS; inhibitor of 20-hydroxyeicosa-tetraenoic acid (20-HETE) production) or 6(Z),15(Z)-20-HED E (antagonist for 20-HETE receptors) mimicked the effects of 17-ODYA on GA responses to elevated PO2, Treatment of vessels with iberiotoxin or glibenc lamide reduced the constriction of the vessels in response to elevated PO2 while treatment with both K+ channel blockers eliminated oxygen-induced con striction of the vessels. Following treatment of GA with indomethacin and 2 0-HETE, the vessels failed to respond to elevated PO2. These results sugges t that oxygen-induced constriction of skeletal muscle resistance arteries r epresents the combined effects of reduced prostanoid release from the vascu lar endothelium and enhanced 20-HETE production in vascular smooth muscle c ells. (C) 2001 Academic Press.