Effect of angiotensin II on Na+/H+ exchangers of the renal tubule

Angiotensin II is a key element in regulating the volume of extracellular l iquid. It acts indirectly through aldosterone secretion by adrenals and dir ectly on the renal tubule too. it regulates luminal Na+/H+ antiporters (NHE 3 and possibly NHE2) after binding to membrane AT(1) receptors located both on the basolateral and on the apical side of the cells. The main site of A ng II action is proximal tubule, mainly the S1 segment which has a high lev el of AT(1) receptors. Circulating Ang ii concentrations (10(-12) to 10(-10 ) M), increased NaCl, water and NaHCO3 reabsorption via NHE3 in the proxima l tubule. There is also a synthesis of Ang II within the cells of proximal tubule, which is secreted within the lumen where the physiological concentr ation is stable 10(-8) M, i.e. 100 to 1000 times higher than the circulatin g concentration. Luminal ANG II originating from kidney has a physiological autocrine function on NaCl, water and probably NaHCO3 reabsorption, since inhibiting Ang II synthesis, by conversion enzyme inhibition, or effect, by AT(1) receptor antagonists, induces a reduction of proximal tubule reabsor ption. The stimulatory effects of circulating and intrarenal Ang it seem to be explained by protein kinase C stimulation and possibly by a reduction o f cAMP production or by a stimulation of a non-receptor tyrosine kinase. When pharmacological doses of Ang II (> 10(-8) M) are applied in the peritu bular or the luminal medium of isolated microperfused proximal tubule in vi tro, a paradoxical inhibition of NHE3 was observed. These effects appear to involve arachidonic acid metabolites through the cytochrome P450 pathway a nd possibly a rise in cytosolic free Ca++. The physiological significance o f these supraphysiological effects are unknown.