Role of Prostaglandins and Arachidonic Acid Derivatives in the Coupling of Cerebral Blood Flow to Cerebral Metabolism

What normally provides tone in the cerebral circulation? What adjusts cerebral blood flow to ce­ rebral metabolism? Why invoke arachidonic acid and its metabolites? The derivatives of arachidonic acid form an ex­ traordinary and bewildering array of compounds of widely differing propertie s. Von Euler ( 1 93 6) created the term to christen the depressor, smooth-muscle-stimulating acidic lipid that he and Goldblatt had demonstrated in human seminal plasma. Bergstrom began to determine the structure of this group of compounds in 1 947 with publication in the early 1 960s (for review , see Bergstrom et aI. , 1 968). Prostaglandins are biosyn­ the sized fro m arachidonic acid and dihomo-y­ linolenic acid , both of which are derived from the essential unsaturated long-chain dietary fatty acids. Arachidonic acid is the predominant substrate for prostaglandin synthesis in the brain. Following the isolation and description of the effects of the pri­ mary and relatively stable prostaglandins (PGF2a , PGE1 , PGE2, PGD2, etc.) came the discovery that prostaglandin synthe s i s was inhibited by the nonsteroidal antiinflammatory age nts such as indomethacin and aspirin (Vane , 1 97 1). Certain dis­ crepancies became apparent in the period 1 970-76 between the effects of prostaglandin synthesis inhi­ bition and the effects of the known endogenous prostaglandins. Then , in rapid succession , came the description of the short-lived derivatives of arachi-