[Molecular mechanism of vascular prostanoid metabolism and circulation control]

Vasoactive prostanoids are produced from arachidonic acid in the arachidonate cascade in various animal cells. In general the cascade is initiated by the reaction of phospholipase A2, and the released arachidonic acid is subjected to oxygenation by either cyclooxygenase or lipoxygenase. The cyclooxygenase reaction produces prostaglandins G2 and H2, the latter of which is further converted to a certain type of prostaglandin and thromboxane A2. 5-Lipoxygenase produces 5-hydroperoxy-arachidonic acid, which is metabolized to leukotrienes B4, C4 and D4. All these enzymes of arachidonate cascade have not necessarily been intensively investigated in vascular tissue. Several papers reported the localization of the arachidonate cascade enzymes in vascular endothelial cells and smooth muscle cells. The use of antibody against prostaglandin I synthase revealed the presence of the enzyme in smooth muscle cells of ovine and rabbit aorta. Arachidonate-specific phospholipase A2 was discovered recently. Localization of the enzyme in human vascular endothelial cells was shown by immunoprecipitation technique. Another recent topic of the arachidonate cascade is a discovery of a cyclooxygenase isoform. A cDNA of the cyclooxygenase-2 was cloned from endothelial cells of human umbilical vein.