Angiotensin II Dose-Dependently Stimulates Human Renal Proximal Tubule Transport by the Nitric Oxide/Guanosine 3′,5′-Cyclic Monophosphate Pathway

Shirai, Ayumi; Horita, Shoko; Nakamura, Motonobu; Satoh, Nobuhiko; Yamada, Hideomi; Suzuki, Masashi; Kudo, Akihiko; Kawakami, Hayato; Hofmann, Franz; Nishiyama, Akira; Kume, Haruki; Enomoto, Yutaka; Homma, Yukio; Seki, George

doi:10.1681/asn.2013060596

Cited by 24 publications

(36 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The institutional review board of the University of Tokyo School of Medicine approved the study and written informed consent was obtained from all subjects as described. 42,44 Measurement of NBCe1 activity in isolated PT The luminally collapsed fresh PT (S2 segment), microdissected manually without collagenase treatment, was incubated with an acetoxymethyl ester form of a pH-sensitive fluorescence dye 2 0 ,7 0 -bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF/AM; Dojindo, Kumamoto, Japan) and cell pH was monitored with a photometry system (OSP-10; Olympus, Tokyo, Japan). Prewarmed (38 1C) Dulbecco's modified Eagle's medium supplemented with 1 mmol/l norepinephrine and equilibrated with 5%CO 2 /95% O 2 gas was used for the peritubular perfusate as described.…”

Section: Human Samplesmentioning

confidence: 99%

“…20,[45][46][47] Bath HCO 3 À reduction (from 25 to 12.5 mmol/l) was repeated two or three times during the control period, and only PTs that showed constant cell pH responses were used for the analysis as described. 44 The NBCe1 activity was determined before and 8 min after insulin addition to the bath perfusate. In some experiments, 100 nmol/l wortmannin (Wako, Tokyo, Japan) was added to the bath perfusate to confirm the role of PI3-K. To compare the results between LETO and OLETF rats or between humans without and with insulin resistance, the basal and insulin-stimulated NBCe1 activities were determined in two to four PTs from each kidney sample and the averaged data were used.…”

Section: Human Samplesmentioning

confidence: 99%

See 1 more Smart Citation

Preserved Na/HCO3 cotransporter sensitivity to insulin may promote hypertension in metabolic syndrome

Nakamura

Yamazaki

Shirai

et al. 2015

Kidney International

Self Cite

View full text Add to dashboard Cite

Hyperinsulinemia can contribute to hypertension through effects on sodium transport. To test whether the stimulatory effect of insulin on renal proximal tubule sodium transport is preserved in insulin resistance, we compared the effects of insulin on abdominal adipocytes and proximal tubules in rats and humans. Insulin markedly stimulated the sodium-bicarbonate cotransporter (NBCe1) activity in isolated proximal tubules through the phosphoinositide 3-kinase (PI3-K) pathway. Gene silencing in rats showed that while insulin receptor substrate (IRS)1 mediates the insulin effect on glucose uptake into adipocytes, IRS2 mediates the insulin effect on proximal tubule transport. The stimulatory effect of insulin on glucose uptake into adipocytes was severely reduced, but its stimulatory effect on NBCe1 activity was completely preserved in insulin-resistant Otsuka Long-Evans Tokushima Fatty (OLETF) rats and patients with insulin resistance. Despite widespread reduction of IRS1 and IRS2 expression in insulin-sensitive tissues, IRS2 expression in the kidney cortex was exceptionally preserved in both OLETF rats and patients with insulin resistance. Unlike liver, acute insulin injection failed to change the expression levels of IRS2 and sterol regulatory element-binding protein 1 in rat kidney cortex, indicating that regulatory mechanisms of IRS2 expression are distinct in liver and kidney. Thus, preserved stimulation of proximal tubule transport through the insulin/IRS2/PI3-K pathway may play an important role in the pathogenesis of hypertension associated with metabolic syndrome.

show abstract

Section: Human Samplesmentioning

confidence: 99%

Section: Human Samplesmentioning

confidence: 99%

Preserved Na/HCO3 cotransporter sensitivity to insulin may promote hypertension in metabolic syndrome

Nakamura

Yamazaki

Shirai

et al. 2015

Kidney International

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, recently, Shirai and colleagues found that in human cells, ANG II, unlike what was observed in other species, induced the dose-dependent and strong stimulation of human proximal tubular transport via the activation of AT1-dependent nitric oxide/guanosine 3', 5'-cyclic monophosphate/ERK [106]. Currently, the molecular mechanisms underlying species-specific differences in proximal tubular responses to the NO/cGMP pathway remain unknown [107].…”

Section: Dose-dependent Biphasic Effects Of Ang II In the Proximal Tumentioning

confidence: 99%

ANG II, ANG-(1-7), ALDO and AVP biphasic effects on Na+/H+ transport: the role of cellular calcium

Mello-Aires¹,

Dellova²,

Castelo‐Branco³

et al. 2017

Nephrol Renal Dis

View full text Add to dashboard Cite

This article reviews the main body of knowledge regarding NHE1 and NHE3 exchangers and their interaction with Angiotensin II, Angiotensin-(1-7), Aldosterone and Arginine Vasopressin, particularly their renal actions. This work addresses the biphasic effects of different hormonal doses on NHE1 or NHE3 in proximal tubule in Wistar, SHR (hypertensives) and their control WKY (normotensives) rats or MDCK cells (which share similarities with the collecting duct). The hormones were applied alone, with their inhibitors or plus agents that change the [Ca 2+ ]i. The data are compatible with hormonal stimulation of these exchangers by increases of [Ca 2+ ]i in lower range, and inhibition at high [Ca 2+ ]i. In MDCK cells and Wistar rats, low doses of ANG II, ALDO or AVP stimulated the exchangers, while high doses inhibited them. ANG-(1-7), in Wistar or WKY rats has inverse, dose-dependent effects. In SHR rats, the biphasic effects of ANG-(1-7) were similar to the effects of ANG II, ALDO or AVP in Wistar rats. The interactions between these effects may represent a mechanism that regulates extracellular volume. In hypertensives animals, a high plasma level of ANG-(1-7) inhibited NHE3 in the proximal tubule, which mitigated hypertension. Figure 6 shows a schematic model to describe these biphasic hormonal effects.

show abstract

“…45 Interestingly, human PTs studied in vitro only exhibit a stimulatory transport response to AngII. 46 …”

Section: Renin Angiotensin System Regulates Pt Nhe3 Distribution and mentioning

confidence: 99%

ISN Forefronts Symposium 2015: Maintaining Balance Under Pressure—Hypertension and the Proximal Tubule

McDonough

2016

Kidney International Reports

View full text Add to dashboard Cite

Renal control of effective circulating volume is key for circulatory performance. When renal Na+ excretion is inadequate, blood pressure rises and serves as a homeostatic signal to drive natriuresis to re-establish effective circulating volume (ECV). Recognizing that hypertension involves both renal and vascular dysfunction, this report concerns proximal tubule Na+/H+ exchanger 3 (PT NHE3) regulation during acute and chronic hypertension. NHE3 is distributed in tall microvilli (MV) in the PT where it reabsorbs a significant fraction of the filtered Na+. NHE3 redistributes, in the plane of the MV membrane, between the MV body, where NHE3 is active, and MV base where NHE3 is less active. High salt diet and acute hypertension both retract NHE3 to the base and reduce PT Na+ reabsorption independent of a change in abundance. The renin angiotensin system provokes NHE3 redistribution independent of blood pressure: the ACE inhibitor captopril redistributes NHE3 to the base and subsequent AngII infusion returns NHE3 to the body of the microvilli and restores reabsorption. Chronic AngII infusion presents simultaneous AngII stimulation and hypertension: NHE3 remains in the body of the MV, due to the high local AngII and inflammation, and exhibits a compensatory decrease in abundance, driven by the hypertension. Genetically modified mice with blunted hypertensive responses to chronic AngII infusion (due to lack of PT AngII receptors, IL-17A or IFN-γ expression) exhibit reduced local AngII accumulation and inflammation and larger decreases in NHE3 abundance which improve the pressure natriuresis responses and reduces the need for elevated BP to facilitate circulating volume balance.

show abstract

Angiotensin II Dose-Dependently Stimulates Human Renal Proximal Tubule Transport by the Nitric Oxide/Guanosine 3′,5′-Cyclic Monophosphate Pathway

Cited by 24 publications

References 48 publications

Preserved Na/HCO3 cotransporter sensitivity to insulin may promote hypertension in metabolic syndrome

Preserved Na/HCO3 cotransporter sensitivity to insulin may promote hypertension in metabolic syndrome

ANG II, ANG-(1-7), ALDO and AVP biphasic effects on Na+/H+ transport: the role of cellular calcium

ISN Forefronts Symposium 2015: Maintaining Balance Under Pressure—Hypertension and the Proximal Tubule

Contact Info

Product

Resources

About