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Treatment with Mesenchymal Stem Cells Improves Renovascular Hypertension and Preserves the Ability of the Contralateral Kidney to Excrete Sodium.

Abstract：

BACKGROUND:Mesenchymal stem cells (MSC) improve renal function and renovascular hypertension in the 2-kidney 1-clip model (2K-1C). While MSC play an immunomodulatory role, induce neoangiogenesis, and reduce fibrosis, they do not correct sodium loss by the contra-lateral kidney. OBJECTIVES:We investigated the tubular function of both stenotic and contralateral kidneys and the effect of MSC treatment by evaluating diuresis, natriuresis, and the expression of the main water and sodium transporters. METHOD:Adult Wistar rats were allocated into four groups: control (CT), CT+MSC, 2K-1C, and 2K-1C+MSC. MSC (2 × 105) were infused through the tail vein 3 and 5 weeks after clipping. Systolic blood pressure (SBP) was monitored weekly by plethysmography. Six weeks after clipping, 24-hour urine and blood samples were collected for biochemical analysis. Gene expression of the Na/H exchanger-3, epithelial sodium channel, Na/K-ATPase, Na/K/2Cl cotransporter, and aquaporins 1 and 2 (AQP1 and AQP2) were analyzed by RT-PCR. Intrarenal distribution of AQP1 and AQP2 was analyzed by immunohistochemistry. RESULTS:In hypertensive 2K-1C animals, MSC prevented additional increases in BP. AQP1, but not AQP2, was suppressed in the contralateral kidney, resulting in significant increase in urinary flow rate and sodium excretion. Gene expressions of sodium transporters were similar in both kidneys, suggesting that the high perfusing pressure in the contralateral kidney was responsible for increased natriuresis. Contralateral hypertensive kidney showed signs of renal deterioration with lower GFR in spite of normal RPF levels. CONCLUSIONS:MSC treatment improved renal function and enhanced the ability of the contralateral kidney to excrete sodium through a tubular independent mechanism contributing to reduce SBP.

journal_name

Kidney Blood Press Res

journal_title

Kidney & blood pressure research

authors

Varela VA,Oliveira-Sales EB,Maquigussa E,Borges FT,Gattai PP,Novaes ADS,Shimoura CG,Campos RR,Boim MA

doi

10.1159/000503346

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

1404-1415

issue

eissn

1420-4096

issn

1423-0143

pii

000503346

journal_volume

pub_type

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Treatment with Mesenchymal Stem Cells Improves Renovascular Hypertension and Preserves the Ability of the Contralateral Kidney to Excrete Sodium.