Site and mechanism of action of diuretics

Abstract

Diuretics have a central role in the treatment of edema and hypertension. This function is primarily an induction of a net negative balance of solute and water. Reviewed herein are the transport properties of each nephron segment that governs salt and water reabsorption with specific reference to the mechanisms by which the various diuretic agents affect those transport processes. Under normal circumstances, the proximal tubule reabsorbs about 50 to 66 percent of the filtered fluid by both active and passive mechanisms. However, diuretics that inhibit proximal reabsorption are "weak" diuretics since distal compensatory mechanisms can overcome their effect. The thin descending limb of Henle is highly permeable to water and relatively impermeable to solutes. Thus, its main physiologic function is to allow osmotic water abstraction. Although diuretics have no direct epithelial effect on this segment, many of the diuretics decrease fluid reabsorption from it by abolishing the papillary osmotic gradient. The decreased water absorption from the descending limb of Henle has a major role in over-all increased diuresis since nephron segments distal to the descending limb are impermeable to water in the absence of vasopressin. The thin ascending limb of Henle is impermeable to water while being highly permeable to sodium and chloride. Diuretics have no direct effect on the thin ascending limb of Henle. The medullary and cortical segments of the thick ascending limb of Henle absorb sodium chloride by active mechanisms as a result of a secondary active chloride transport mechanism that depends on the presence of sodium (co-transport mechanism). This transport mechanism is located on the luminal membrane. Most of the "loop" diuretics effect this process from the luminal side by having a direct inhibitory effect on this co-transport process. The diuretics that have a primary effect on the medullary segment (furosemide, bumetanide, ethacrynic acid) inhibit the concentrating mechanisms, whereas the diuretics that are effective primarily in the cortical segment (thiazides plus the diuretics affecting the medullary segment) inhibit the urinary diluting mechanism. The loop diuretics are physiologically the most potent family of diuretics. The cortical collecting duct segment reabsorbs sodium by active mechanisms. These processes are stimulated by aldosterone. The diuretics that affect these processes are considered weak diuretics, but they do have the metabolic effect of potassium sparing.(ABSTRACT TRUNCATED AT 400 WORDS)