Renal Microvascular Rarefaction Accompanies Interstitial Fibrosis and Tubular Damage in One Kidney‐Deoxycorticosterone Acetate‐Salt (1K/DOCA/salt)‐Dependent Hypertension

Abstract

High dietary salt intake is a risk factor for hypertension and chronic kidney disease. However, the mechanisms involved remain poorly understood. Microvascular rarefaction ‐ defined as the loss of arterioles and capillaries within a tissue ‐ has the potential to increase total peripheral vascular resistance and cause local hypoxia and tissue damage. Here we utilised one kidney‐deoxycorticosterone acetate‐salt (1K/DOCA/salt)‐treated mice to investigate whether the development of hypertension and renal damage are associated with microvascular rarefaction. C57BL6/J mice were uninephrectomised and treated for 21 d with DOCA (2.4 mg/day, s.c.) and 0.9% NaCl in the drinking water. Normotensive controls were uninephrectomized and received a placebo pellet and normal drinking water (1K/placebo). Blood pressure (BP) was measured via tail cuff; renal vascular density was assessed immunohistochemically as the percentage area of CD31‐positive staining; renal collagen was detected with picrosirius red; and hematoxylin and eosin were used to visualise renal inflammation and histopathology. 1K/DOCA/salt‐treated mice had higher BPs (160±4 vs. 126±4 mmHg; n≥7; P≤0.0001) and renal weights (321±16 vs. 251±13 mg; n≥7; P<0.05) than 1K/placebo mice. 1K/DOCA/salt‐treated mice also displayed marked renal fibrosis, inflammation and damage as evidenced by a 10‐fold increase in interstitial collagen (n≥7; P<0.05), the presence of inflammatory cells, tubular dilatation and atrophy, and a loss of epithelial brush borders. Importantly, 1K/DOCA/salt‐treatment was associated with a 50% reduction in microvascular density (n≥7; P<0.05), mainly due to a loss of peritubular capillaries. Correlation analyses revealed a trend for an inverse association of peritubular capillary density with collagen deposition (n≥7; r= −0.7058; P= 0.117), but not with BP or inflammatory cell infiltration. Low magnification analysis of kidney sections revealed that peritubular capillary loss occurred in bands emanating from the arcuate arteries. Moreover, collagen deposition, inflammatory cell infiltration and tubular atrophy displayed a similar banding pattern. In summary, these studies reveal a likely association between microvascular rarefaction and fibrosis during the development of 1K/DOCA/salt‐dependent hypertension and renal damage. Future studies will assess whether strategies aimed at maintaining renal microvascular density can minimise renal fibrosis and damage.Support or Funding InformationThe work was funded by the National Health and Medical Research Council of Australia (GNT1143674)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.