Renal Effects of Prostaglandins and Cyclooxygenase-2 Inhibitors

Prostaglandins (PGs) with best-defined renal functions are PGE(2) and prostacyclin (PGI(2)). These vasodilatory PGs increase renal blood flow and glomerular filtration rate under conditions associated with decreased actual or effective circulating volume, resulting in greater tubular flow and secretion of potassium. Under conditions of decreased renal perfusion, the production of renal PGs serves as an important compensatory mechanism. PGI(2) (and possibly PGE(2)) increases potassium secretion mainly by stimulating secretion of renin and activating the renin-angiotensin system, which leads to increased secretion of aldosterone. In addition, PGE(2) is involved in the regulation of sodium and water reabsorption and acts as a counterregulatory factor under conditions of increased sodium reabsorption. PGE(2) decreases sodium reabsorption at the thick ascending limb of the loop of Henle probably via inhibition of the Na(+)-K(+)-2Cl(-) cotransporter type 2 (NKCC2). Cyclooxygenase inhibitors may enhance urinary concentrating ability in part through effects to upregulate NKCC2 in the thick ascending limb of Henle's loop and aquaporin-2 in the collecting duct. Thus, they may be useful to treat Bartter's syndrome and nephrogenic diabetes insipidus.