Stem Cells Improved Renovascular Hypertension Independently of the Change of Renal Water and Sodium Transporters

Abstract

Mesenchymal stem cells (MSC) improved renal morphology, inflammation, microvascular rarefaction, fibrosis and proteinuria in the stenotic kidney of 2Kidney‐1Clip (2K‐1C) model. Here, we investigated the effect of MSC on tubular function by evaluating the expression of the water and sodium transporters in the clipped kidney. Adult male Wistar rats were divided into groups: Control, Control+MSC, 2K‐1C, 2K‐1C+MSC. MSC was infused in the 3rd week after clipping into the tail vein (2x105 cells) with an interval of 2 weeks. Tail blood pressure (BP) was monitored weekly. Six weeks after clipping, 24 hours urine and blood were collected for biochemical analysis. Gene expression of the Na/Hexchanger (NHE3), sodium channel (ENaC), Na/KATPase, Na/K/2Cl cotransporter and aquaporins1 and 2 (AQP1 and AQP2).The 2K‐1C animals showed gradual increase of BPwhich was prevented by MSC treatment.There was a rise in the diuresis in the 2K‐1C rats, in parallel with a reduction in the AQP1 in the medullae but not in the cortex. Sodium excretion was reducedin spite of a decrease in ENaC expression with no changes in the other sodium transporters. This phenomenon may be explained by the increase in the free water excretion. Vascular rarefaction in the medulla (previously observed) together with the reduction in the expression of AQP1,mainly in the medulla suggests a deficit in the concentrating ability of the stenotic kidney. MSC did not corrected these tubular transport defects. Thus, MSC treatment was effective to minimize the renovascular hypertension and microvascular loss, however it was not sufficient to improve the concentrating ability of the stenotic kidney. Supported by FAPESP.