Modulation by locally produced luminal angiotensin II of proximal tubular sodium reabsorption via an AT₁ receptor

Abstract

The concentration of angiotensin II reported in proximal tubular fluid in anaesthetized rats is considerably higher than in plasma, indicating secretion of this peptide into the tubular lumen. Shrinking split-drop micropuncture was used to examine the effect of endogenous angiotensin on sodium and water absorption in the proximal convoluted tubule. Addition of losartan, a nonpeptide AT, receptor blocker, to intratubular fluid increased fluid uptake by 15.7+3.9% (10-' M) and 24.7+9.4% (10-4 M) whereas the AT2 inhibitor, PD123319 had no effect. We conclude that angiotensin II is secreted into proximal tubular fluid and, in the anaesthetized rat, is maintained at a concentration that inhibits sodium and water transport via AT, receptors.

Effects of angiotensin II receptor blockade on proximal fluid uptake in the rat kidney

“…All three antagonists, losartan, EXP3174 and candesartan at 10 78 M decreased¯uid absorption by approximately 20%. At a higher concentration (10 75 M), both EXP3174 and candesartan decreased¯uid absorption, in contrast with previous observations that losartan at this dose increases transepithelial sodium transport (Hiranyachattada & Harris, 1996;Leyssac et al, 1997). The dose-dependent, biphasic eect of losartan is not consistent with selective blockade of luminal AT 1 receptors, and suggests that losartan at high concentrations (410 76 M) has a nonselective eect on sodium absorption.…”

“…Samples of luminal fluid obtained by micropuncture from superficial proximal tubules have been shown to contain a nanomolar concentration of angiotensin II ( Seikaly et al ., 1990 ; Braam et al ., 1993 ; Mitchell et al ., 1997 ). Previous studies in our laboratory ( Hiranyachattada & Harris, 1996 ) and by Leyssac et al . (1997) concluded that addition of a high concentration of the AT 1 antagonist losartan (10 −5 M ) to the proximal tubule lumen enhanced fluid uptake.…”

“…Samples of luminal¯uid obtained by micropuncture from super®cial proximal tubules have been shown to contain a nanomolar concentration of angiotensin II (Seikaly et al, 1990;Braam et al, 1993;Mitchell et al, 1997). Previous studies in our laboratory (Hiranyachattada & Harris, 1996) and by Leyssac et al (1997) concluded that addition of a high concentration of the AT 1 antagonist losartan (10 75 M) to the proximal tubule lumen enhanced¯uid uptake. Taken together these observations support the existence of high endogenous concentrations of angiotensin II within the luminal¯uid, and suggest that, at least in the anaesthetized rat,¯uid uptake is suppressed by the endogenous concentration of angiotensin II in the lumen.…”

“…We used the AT 1 receptor antagonists, losartan, EXP3174 (a potent active metabolite of losartan) and candesartan, as the predominant angiotensin receptor in the proximal tubule has been reported to be the AT 1 subtype ( Sechi et al ., 1992 ). A previous study from this laboratory supports this conclusion since AT 2 receptor blockade with PD‐123319 did not affect fluid uptake ( Hiranyachattada & Harris, 1996 ).…”

Regulation of the renal proximal tubule second sodium pump by angiotensins

“…Burns et al (34) showed that over 80% of the Ang II receptors found in the basolateral membrane of proximal tubules from rat and rabbit kidneys are of the AT 1 type, with the other 20% being of the AT 2 type. In general, it is accepted that the stimulatory effect of Ang II on proximal tubule Na + reabsorption is mediated by losartan-sensitive AT 1 receptors located in both luminal and basolateral membranes (15,35).…”