The relation between pericyte detachment and interstitial fibrosis in dahl salt-sensitive hypertensive (dahls) rats

Background: Congestive heart failure produces the state of fluid volume overload, central venous pressure (CVP) elevation, and consequently renal venous pressure (RVP) elevation. We have recently developed a novel rat unilateral renal venous congestion model, in which ligation of the inferior vena cava between both renal veins artificially induced renal congestion in the left kidney only. In this model, pericyte detachment and pericyte-myofibroblast transition (PMT) around the vasa recta were involved in interstitial injury and fibrosis. Dahl salt-sensitive hypertensive (DahlS) rats on high salt diets exhibit hypertension, congestive heart failure, fluid volume overload, CVP and RVP elevation, and renal damage, considering to be a non-artificial renal congestion model. The relation, however, between renal interstitial injury and fibrosis, elevated RVP, and pericyte detachment in DahlS rats has not been reported. In the present study, we assessed the relation of pericyte detachment around the vasa recta and PMT with interstitial fibrosis in DahlS rats. Methods: Eight-week-old DahlS rats (Dahl/Mcwi) were divided into three groups: normal diet, 4% NaCl diet, and 8% NaCl diet groups, and their kidneys were analyzed after 2 weeks. Total mRNA and protein expression levels were quantified by real-time PCR and western blot, respectively. Tubulointerstitial damage and fibrosis were identified by histological analysis. Furthermore, we evaluated pericyte detachment around the vasa recta by low-vacuum scanning electron microscopy (LV-SEM). Results: The expression of KIM1, a tubulointerstitial damage marker; CNN1 and αSMA, interstitial fibrosis markers; and TAGLN, a smooth muscle protein22 and PMT marker; was significantly increased in a salt-dependent manner in DahlS rats. In histological analysis, hyperplasia of the extracellular matrix and renal tubular injury were detected in 4% and 8% NaCl diet groups. The positive area of PMT markers in the interstitial space around the vasa recta was also increased in the NaCl diet groups. Pericyte detachment from the vasa recta was observed in the NaCl diet groups by LV-SEM. Conclusions: Pericyte detachment and PMT are involved in tubulointerstitial injury and fibrosis of DahlS rats. Renal venous congestion and subsequent physiological changes could have a role in renal damage and fibrosis. Arterial hypertension has been emphasized for a long time in renal injury, and venous hypertension must also be focused on with the concept of renal congestion. Further understanding of this concept may lead to new therapeutic strategies for renal injury.