[Effect of angiotensin ii on Na+/H+ exchangers of the renal tubule].
Angiotensin II is a key element in regulating the volume of extracellular liquid. It acts indirectly through aldosterone secretion by adrenals and directly on the renal tubule too: It regulates luminal Na+/H+ antiporters (NHE3 and possibly NHE2) after binding to membrane AT1 receptors located both on the basolateral and on the apical side of the cells. The main site of Ang II action is proximal tubule, mainly the S1 segment which has a high level of AT1 receptors. Circulating Ang II concentrations (10(-12) to 10(-10) M), increased NaCl, water and NaHCO3 reabsorption via NHE3 in the proximal tubule. There is also a synthesis of Ang II within the cells of proximal tubule, which is secreted within the lumen where the physiological concentration is stable 10(-8) M, i.e. 100 to 1000 times higher than the circulating 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 AT1 receptor antagonists, induces a reduction of proximal tubule reabsorption. The stimulatory effects of circulating and intrarenal Ang II seem to be explained by protein kinase C stimulation and possibly by a reduction of 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 peritubular or the luminal medium of isolated microperfused proximal tubule in vitro, a paradoxical inhibition of NHE3 was observed. These effects appear to involve arachidonic acid metabolites through the cytochrome P450 pathway and possibly a rise in cytosolic free Ca++. The physiological significance of these supraphysiological effects are unknown.
Poggioli
J
J
INSERM U356, Paris.
Karim
Z
Z
Paillard
M
M
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*
D011945:Receptors, Angiotensin; D017923:Sodium-Hydrogen Exchangers; D000804:Angiotensin II
Effet de l'angiotensine II sur les échangeurs Na+/H+ du tubule rénal.