Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: REGULATION OF RENAL TUBULAR SODIUM TRANSPORT BY ANGIOTENSIN II AND ATRIAL NATRIURETIC FACTOR

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Abstract
SUMMARY: The effects of angiotensin II (AngII) on water and electrolyte transport are biphasic and dose‐dependent, such that low concentrations (10−12 to 10−9 mol/L) stimulate reabsorption and high concentrations (10−7 to 10−6 mol/L) inhibit reabsorption. Similar dose‐response relationships have been obtained for luminal and peritubular addition of AngII. The cellular responses to AngII are mediated via AT1 receptors coupled via G‐regulatory proteins to several possible signal transduction pathways. These include the inhibition of adenylyl cyclase, activation of phospholipases A2, C or D and Ca2+ release in response to inositol‐1,4,5,‐triphosphate or following Ca2+ channel opening induced by the arachidonic acid metabolite 5,6,‐epoxy‐eicosatrienoic acid. In the brush border membrane, transduction of the AngII signal involves phospholipase A2, but does not require second messengers. Angiotensin II affects transepithelial sodium transport by modulation of Na+/H+ exchange at the luminal membrane and Na+/HCO3 cotransport, Na+/K+‐ATPase activity and K+ conductance at the basolateral membrane. Atrial natriuretic factor (ANF) does not appear to affect proximal tubular sodium transport directly, but acts via specific receptors on the basolateral and brush border membranes to raise intracellular cGMP levels and inhibit AngII‐stimulated transport. It is concluded that there is a receptor‐mediated action of ANF on proximal tubule reabsorption acting via elevation of cGMP to inhibit AngII‐stimulated sodium transport. This effect is exerted by peptides delivered at both luminal and peritubular sides of the epithelium and provides a basis for the modulation by ANF of proximal glomerulotubular balance. The evidence reviewed supports the concept that in the proximal tubule, AngII and ANF act antagonistically in their roles as regulators of extracellular fluid volume.