Control of ENaC-Mediated Sodium Reabsorption in the Distal Nephron by Bradykinin

Chronic Overexpression of Bradykinin in Kidney Causes Polyuria and Cardiac Hypertrophy

“…Furthermore, the urine of KapBK rats is diluted with regards to several other components like protein content, sodium, potassium, and urea suggesting reduction of water reabsorption (Figure 2B). Analyzing daily sodium and potassium excretion, we noted an increased sodium excretion and an increased Na + /K + excretion ratio (Figure 2C) in agreement with previous studies (7, 15, 31, 32). No changes were observed regarding plasma levels of proteins, creatinine, sodium or potassium (Figure 2D), and blood cell count (Table S1) and only body composition analysis (Figure S1) showed a trend to increased water content.…”

“…However, the measurements of Na + , Cl − , and K + in urine indicated that only Na + showed increased excretion in KapBK rats, suggesting that the inhibition of Na + reabsorption is not due to cotransporters such as Na/K-ATPase, thiazide-sensitive sodium chloride co-transporter (NCCT) or sodium-potassium-chloride co-transporter (NKCC2), all of them important sodium transporters in the apical membrane of different regions of the nephrons (50). Together with previous studies demonstrating that BK inhibits only ENaC (7, 15, 17, 32), the here presented reduction of the gene expression of ENaC subunits, and the urine concentration of the excreted ions together indicate that the observed natriuresis in KapBK rats is caused by reduction of ENaC, at least partially on the level of gene expression.…”

“…These effects were observed after acute BK treatment in kidney (17) but also in studies searching for chronic effects (36). Furthermore, the DNA construct was designed to be expressed in proximal tubules and to secrete BK into the extracellular space, based on the signal peptide present in the expressed protein and the ubiquitous expression of furin, and it is well-established that intraluminally generated kinins in kidney exert autocrine and paracrine actions on distal tubular cells, favoring natriuresis and diuresis (32) as observed in the present study. In addition, interstitially released BK contributes to the regulation of cortical and medullary blood flow (38), as was also observed in KapBK rats and will be discussed below.…”

“…Acute infusion of bradykinin in the kidneys causes polyuria inhibiting vasopressin activity in collecting tubules (17, 18, 34) and increasing sodium excretion (1, 7, 9, 10, 15, 32, 35). However, the consequences of chronic BK excess in the kidneys are still incompletely studied (36, 37).…”

“…Again, these new data suggest that the inhibition of ENaC activity by BK infusion can be induced by gene expression regulation. It is well-established that the increase in UNaV by BK is due to the inhibition of ENaC (7, 15, 32). Other authors have shown inhibition of sodium reabsorption by BK (7, 31, 49).…”