Pericyte detachment and renal congestion involve interstitial injury and fibrosis in Dahl salt-sensitive rats and humans with heart failure.

Congestive heart failure produces fluid volume overload, central and renal venous pressure elevation, and consequently renal congestion, which results in worsening renal function. Pericyte detachment and pericyte-myofibroblast transition (PMT) were linked to renal interstitial fibrosis. Dahl salt-sensitive hypertensive (DahlS) rats are a non-surgical renal congestion model. The relation, however, between renal interstitial damage, pericyte morphology, and PMT in the renal congestion of DahlS rats has not been reported. DahlS rats (8-week-old) were fed normal salt (NS, 0.4% NaCl) or high salt (HS, 4% NaCl), and the left kidney was decapsulated to reduce renal interstitial hydrostatic pressure (RIHP) at 9 weeks old. One week after capsulotomy, both kidneys were analyzed by molecular and histological techniques. Renal pericyte structure was assessed in the body donors with/without venous stasis. Markers of tubulointerstitial damage, interstitial fibrosis, and PMT were upregulated in the right non-decapsulated kidney of DahlS rats fed HS. Renal tubular injury and fibrosis were detected in the HS diet groups in histological analysis. Pericyte detachment was observed in the right non-decapsulated kidney of DahlS rats fed HS by low vacuum-scanning electron microscopy. Decapsulation in DahlS rats fed HS attenuated these findings. Also, renal pericytes detached from the vascular wall in patients with heart failure. These results suggest that pericyte detachment and PMT induced by increased RIHP are responsible for tubulointerstitial injury and fibrosis in DahlS rats and humans with renal congestion. Renal venous congestion and subsequent physiological changes could be therapeutic targets for renal damage in cardiorenal syndrome.