Early damage in 2K1C hypertension is driven by cytokine generation of parenchymal cells

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The objective of this study was to define a role for chemokine generation by parenchymal cells versus circulating inflammatory cells in the initiation of renal damage in the 2K1C model of renovascular hypertension. 129 SV mice were subjected to renal artery stenosis (RAS) by placement of a polytetraethylene cuff on the right renal artery. Systolic blood pressure increased within 2 days of surgery. The cuffed kidney developed tubular atrophy, whereas the contralateral kidney developed compensatory enlargement. Immunohistochemical staining of the cuffed kidney revealed less than 2 CD3+ T cells per 200x field, and rare F4/80+ macrophages or CD20+ B cells in the first 2 weeks following RAS, with progressive increases in macrophages and T cells throughout the 6‐week observation period. Despite the relative paucity of infiltrating inflammatory cells, there was a dramatic increase in chemokine generation within the first week following RAS, as assessed by qPCR analysis of renal cortical homogenates, with 25‐fold induction of MCP‐1, 47‐fold induction of RANTES, and 15‐fold induction of MIP‐2. Chemokine generation continued to increase throughout the 6 weeks, during which circulating inflammatory cells infiltrated the cuffed kidney. Increased expression of MCP‐1 was detected in tubular epithelial cells within 1 week of RAS. We conclude that chemokine generation precedes inflammatory cell influx in RAS.