Cardiovascular and Renal Actions of Cytochrome P-450 Metabolites of Arachidonic Acid

Cytochrome P-450 is the terminal oxidase of the electron transport chain in the endoplasmic reticulum. Arachidonic acid (AA) can be oxidatively metabolized by cytochrome P-450 hemoproteins to an array of compounds identified as constituents of tissues and biological fluids. Their synthesis can be manipulated by pharmacologic probes and are altered in pathophysiologic conditions. These novel eicosanoids stimulate release of peptide and steroid hormones, inhibit platelet and leukocyte aggregation, influence Na+-K+-ATPase and alter vasomotor tone. They also participate in fluid and electrolyte homeostasis, stimulus-secretion coupling, and regulation of tissue blood flow. Since these novel AA metabolites may participate in receptor-mediated signal transduction, and have been implicated in the generation of second messengers and changes in intracellular calcium, these studies have important implications for understanding basic biological mechanisms