Hydrochlorothiazide treatment increases the abundance of the NaCl cotransporter in urinary extracellular vesicles of essential hypertensive patients

Mar 10, 2017American journal of physiology. Renal physiology

Hydrochlorothiazide treatment raises levels of salt transporter in urine particles of patients with high blood pressure

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Abstract

Hydrochlorothiazide treatment resulted in significantly increased abundance of NCC isoforms 1 and 2 and phosphorylated NCC in urinary extracellular vesicles from essential hypertensive patients.

NCC detected in human urinary extracellular vesicles has a structure similar to that found in human kidney membranes.
The abundance of total NCC and phosphorylated NCC increased in patients treated with hydrochlorothiazide.
Valsartan treatment did not show a significant increase in NCC abundance or phosphorylation.
The increase in NCC levels in urinary extracellular vesicles correlates with the blood pressure response to hydrochlorothiazide.

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The thiazide-sensitive NaCl cotransporter (NCC), located apically in distal convoluted tubule epithelia, regulates the fine-tuning of renal sodium excretion. Three isoforms of NCC are generated through alternative splicing of the transcript, of which the third isoform has been the most extensively investigated in pathophysiological conditions. The aim of this study was to investigate the effect of different anti-hypertensive treatments on the abundance and phosphorylation of all three NCC isoforms in urinary extracellular vesicles (uEVs) of essential hypertensive patients. In uEVs isolated from patients (= 23) before and after hydrochlorothiazide or valsartan treatment, the abundance and phosphorylation of the NCC isoforms was determined. Additionally, clinical biochemistry and blood pressure of the patients was assessed. Our results show that NCC detected in human uEVs has a glycosylated and oligomeric structure, comparable to NCC present in human kidney membrane fractions. Despite the inhibitory action of hydrochlorothiazide on NCC activity, immunoblot analysis of uEVs showed significantly increased abundance of NCC isoforms 1 and 2 (NCC), total NCC (NCC), and the phosphorylated form of total NCC (pNCC-T55/T60) in essential hypertensive patients treated with hydrochlorothiazide but not with valsartan. This study highlights that NCC, NCC, and pNCC-T55/T60 are upregulated by hydrochlorothiazide, and the increase in NCC abundance in uEVs of essential hypertensive patients correlates with the blood pressure response to hydrochlorothiazide. n1/2 1-3 1-3 1/2 1-3 1-3

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Hydrochlorothiazide treatment increases the abundance of the NaCl cotransporter in urinary extracellular vesicles of essential hypertensive patients

Abstract

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