REGULATION OF RENAL TUBULAR SODIUM-TRANSPORT BY ANGIOTENSIN-II AND ATRIAL-NATRIURETIC-FACTOR

1. The effects of angiotensin II (AngII) on water and electrolyte tran sport are biphasic and dose-dependent, such that low concentrations (1 0(-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. 2, The cellular responses to AngII are mediated via AT(1) re ceptors coupled via G-regulatory proteins to several possible signal t ransduction pathways, These include the inhibition of adenylyl cyclase , activation of phospholipases A(2), C Or D and Ca2+ release ire respo nse 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 i nvolves phospholipase A(2), but does not require second messengers, 3, 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, 4. 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 cG MP levels and inhibit AngII-stimulated transport, 5, It is concluded t hat there is a receptor-mediated action of ANF on proximal tubule reab sorption acting via elevation of cGMP to inhibit AngII-stimulated sodi um transport, This effect is exerted by peptides delivered at both lum inal and peritubular sides of the epithelium and provides a basis for the modulation by ANF of proximal glomerulotubular balance, The eviden ce reviewed supports the concept that in the proximal tubule, AngII an d ANF act antagonistically in their roles as regulators of extracellul ar lull volume.