Renal prostaglandin synthesis: Sites of production and specific actions of prostaglandins

Abstract

Prostaglandins are substances that exert their effects at the site of their production. Therefore, the synthesis and effects of prostaglandins have to be considered separately for each nephron segment. In the cortex, major sites of prostaglandin synthesis include arteries and arterioles as well as the glomerulus. At these sites, prostaglandins are important in maintaining blood flow and glomerular filtration, especially during conditions of enhanced vasoconstrictor activity. Vasoconstrictors such as angiotensin II, norepinephrine, and vasopressin increase production of the vasodilator prostaglandins, thereby preventing an overshoot of their action. The role of arteriolar-glomerular prostaglandins in maintaining blood flow and filtration may be even more prominent during renal diseases. The proximal tubule and the loop of Henle show little ability to produce prostaglandins, but may generate considerable amounts of epoxygenase products of arachidonic acid. These epoxygenase products may play a prostaglandin-independent role in water and electrolyte transport in the thick ascending loop of Henle and the collecting tubule. Both the cortical and the medullary collecting tubules produce large amounts of prostaglandins, predominantly prostaglandin E 2 (PGE 2). In these segments, synthesis of PGE 2 is stimulated by bradykinin and to a somewhat more variable degree by vasopressin. The PGE 2 generated antagonizes the hydroosomotic effect of vasopressin both in vivo and in vitro, and may influence electrolyte excretion. Thus, the overall role of PGE 2—and possibly of epoxygenase products of arachidonic acid—in tubular functions seems to be one of local modulation of water and electrolyte transport. Finally, interstitial cells are a major site of medullary prostaglandin production. Prostaglandins generated by the interstitial cells may play a role in maintaining blood flow to this poorly oxygenated and hypertonic region of the kidney.