Angiotensin II and hypertonicity modulate proximal tubular aquaporin 1 expression

Abstract

Aquaporin 1 (AQP1) is the major water channel in the renal proximal tubule (PT) and thin descending limb of Henle, but its regulation remains elusive. Here, we investigated the effect of ANG II, a key mediator of body water homeostasis, on AQP1 expression in immortalized rat proximal tubule cells (IRPTC) and rat kidney. Real-time PCR on IRPTC exposed to ANG II for 12 h revealed a biphasic effect AQP1 mRNA increased dose dependently in response to 10 Ϫ12 to 10 Ϫ8 M ANG II but decreased by 50% with 10 Ϫ7 M ANG II. The twofold increase of AQP1 mRNA in the presence of 10 Ϫ8 M ANG II was abolished by the AT1 receptor blocker losartan. Hypertonicity due to either NaCl or mannitol also upregulated AQP1 mRNA by threeand twofold, respectively. Immunocytochemistry and Western blotting revealed a two-to threefold increase in AQP1 protein expression in IRPTC exposed concomitantly to ANG II (10 Ϫ8 M) and hypertonic medium (either NaCl or mannitol), indicating that these stimuli were not additive. Three-dimensional reconstruction of confocal images suggested that AQP1 expression was increased by ANG II in both the apical and basolateral poles of IRPTC. In vivo studies showed that short-term ANG II infusion had a diuretic effect, while this effect was attenuated after several days of ANG II infusion. After 10 days, we observed a twofold increase in AQP1 expression in the PT and thin descending limb of Henle of ANG II-infused rats that was abolished when rats were treated with the selective AT 1-receptor antagonist olmesartan. Thus ANG II increases AQP1 expression in vitro and in vivo via direct interaction with the AT 1 receptor, providing an important regulatory mechanism to link PT water reabsorption to body fluid homeostasis via the renin-angiotensin system. renin angiotensin system; proximal tubule ANG II, the major effector of the renin-angiotensin system (RAS) (37), plays direct and indirect roles in water and salt homeostasis. In addition to its regulation of renal blood flow, glomerular filtration, and aldosterone secretion, ANG II binding to ANG II type 1 receptors (AT 1 R) located in kidney proximal tubules additionally modulates sodium and bicarbonate reabsorption (22). AT 1 R is broadly distributed in the kidney vasculature and the proximal tubule, medullary thick ascending limb, and all segments of the collecting duct (45-47). Lee et al. (39) demonstrated that ANG II can potentiate aquaporin 2 (AQP2) membrane insertion in response to vasopressin and that this effect can be blocked by candesartan, an AT 1 R blocker, in primary cultured rat inner medullary collecting duct cells. Furthermore, ANG II was also shown to downregulate the expression of the urea transporter UT-A1, as well as that of the vasopressin-sensitive water channel AQP2 (35) in the rat kidney. In addition, ANG II upregulates vasopressin receptor type 2 (V2R) expression in the rat (68). Thus ANG II appears to play an important role in water reabsorption via its direct and indirect actions on regulation of the vasopressin-sensitive water channel AQP2...

Effect of high-salt diet on mean arterial pressure, renal epithelial sodium channels and aquaporin subunits expression levels in Spontaneously Hypertensive Rats

“…However, the HS diet in the present study showed downregulation of both mRNA and protein levels of AQP1 (Fig 5A and 7A). These observations could be due to the suppression of RAS by HS diet as Ang II has been reported to increases AQP1 expression in the proximal tubule via direct interaction with angiotensin type 1 receptor [81]. While, all the RAS components are expressed in renal proximal tubule cells [82] suppression of the function of RAS by HS diet may lead to low production of Ang II [83], which has been associated with the downregulation of AQP1 and AQP2 [79].…”

Aquaporin Changes during Diabetic Retinopathy in Rats Are Accelerated by Systemic Hypertension and Are Linked to the Renin-Angiotensin System

“…[21][22][23] In our previous reports, we showed that changes in the expression and distribution of AQP1,4 occur during the early stages of DR. 24,25 Few studies have focused on the mechanism of how AQP1,4 changes as DR progresses. The RAS is involved deeply in the regulation of AQP1 expression in renal disorders, 26,27 and treatment with an ARB slows the progression of chronic kidney disease in patients with diabetes by regulating medullary transport proteins, including AQP2. 28 However, to our knowledge the relationship between the RAS and AQP1,4 in the central nervous system has not been investigated.…”

Modulation of aquaporin 2 expression in the kidney of young goats by changes in nitrogen intake

“…In an immortalised rat proximal tubule cell line and in rat kidney, angiotensin II (Ang II) was able to increase AQP1 mRNA and protein expression (Bouley et al 2009). In principle, changes in dietary protein content are able to modulate Ang II concentrations.…”

“…Furthermore, AQP1 mRNA and protein were upregulated by extracellular hypertonicity in immortalised rat proximal tubule cells (Bouley et al 2009). Water intake of individual goats was not monitored in the current study.…”