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

Abstract

1 Angiotensin II has a well described dose-dependent biphasic action on proximal tubule¯uid uptake, although the concentration and eect of endogenous luminal angiotensin II remain controversial. 2 Shrinking split-droplet micropuncture was used to examine the¯uid uptake in response to the luminal application of three AT 1 antagonists (losartan, EXP3174, candesartan). 4 All three antagonists at a low concentration (10 78 M) decreased¯uid uptake. EXP3174 and candesartan at a higher concentration (10 75 M) also decreased¯uid uptake in contrast to the previously reported eect of losartan. 5 We conclude that the endogenous concentration of antiotensin II in the proximal luminal¯uid is low and exerts a stimulatory eect on¯uid absorption. Losartan at concentrations greater than 10 76 M may have a non-selective action on¯uid uptake.

Angiotensin II-induced hypertensive renal inflammation is mediated through HMGB1-TLR4 signaling in rat tubulo-epithelial cells

“…However, the mechanisms by which hypertension contributes to the progression of renal injury is not clear. In this study, we observed that AngII exposure resulted in significant up-regulation of TNFα and IL-1β in NRK52E cells after 6 h. Our results are consistent with those of previous studies which have shown that AngII infusion increases the production of PIC in rat kidneys [53][54][55]. Although previous studies have investigated the effects of AngII on kidneys, the upstream signaling mechanism are not well understood.…”

Acute Effects of Candesartan on Rat Renal Haemodynamics and Proximal Tubular Reabsorption

“…17,18 In a previous study using in vivo spilt-droplet micropuncture, luminal injection of candesartan inhibited fluid transport by 20%. 19 The degree of reduction of proximal fluid transport by candesartan when estimated by lithium clearance was less than that reported using microperfusion, perhaps because changes in lithium clearance reflect effects in all proximal tubules rather than only in superficial nephrons. This interpretation is supported by a study using both intravenous injection and proximal microperfusion of the AngII receptor antagonist DuP753.…”

“…Inhibition of proximal fluid transport by intravenous infusion of candesartan may be mediated by blockade of receptors at either luminal or peritubular sites and AT 1 receptors have been reported on both luminal and basolateral membranes of proximal tubule cells 17,18 . In a previous study using in vivo spilt‐droplet micropuncture, luminal injection of candesartan inhibited fluid transport by 20% 19 . The degree of reduction of proximal fluid transport by candesartan when estimated by lithium clearance was less than that reported using microperfusion, perhaps because changes in lithium clearance reflect effects in all proximal tubules rather than only in superficial nephrons.…”

Angiotensin II mediates downregulation of aquaporin water channels and key renal sodium transporters in response to urinary tract obstruction

“…Subsequently, cAMP activates protein kinase A, which phosphorylates various proteins including AQP2 and the type 1 bumetanidesensitive Na-K-2Cl cotransporter (NKCC2 ) (7,16,46). ANG II also stimulates aldosterone secretion and increases sodium and bicarbonate reabsorption in the kidney proximal tubule via AT 1 receptors (18,35,52,53). Several studies have demonstrated that ANG II also has an important effect on the TAL and collecting duct in addition to the proximal tubules (2,35).…”