Monocyte chemoattractant protein-1 and macrophage infiltration in hypertensive kidney injury

Background. We investigated whether monocyte chemoattractant protein-1 (MCP-1) is expressed in hypertensive nephrosclerosis, and tested the effect of angiotensin II type 1 receptor blockade on MCP-1 expression and macrophage (M Phi) infiltration. Methods. Rats with two-kidney, one-clip (2K1C) hypertension with and without treatment with the angiotensin II type 1 receptor antagonist valsartan (3 mg/kg/day) were studied. In these animals as well as in spontaneously hypertensive rats (SHR), stroke-prone SHR (SHR-SP), hypertensive mRen-2 transgenic rats (TGR), and respective control strains, MCP-1 expression in the kidney was investigated by Northern and Western blots and by immunohistochemistry. Glomerular and interstitial M Phis were counted. Results. In the nonclipped kidney of 2K1C rats, MCP-1 expression was elevated at 14 and 28 days when significant M Phi infiltration was present. MCP-1 was localized to glomerular endothelial and epithelial cells, interstitial and tubular cells, M Phis, and vascular smooth muscle cells. A similar pattern of MCP-1 staining was present in TGR kidneys, whereas MCP-1 expression was not increased in SHR and SHR-SP. Valsartan reduced but did not normalize brood pressure, blocked the induction of MCP-1 protein in 2K1C kidneys, and decreased interstitial M Phi infiltration significantly. Conclusion. MCP-1 expression is increased in angiotensin II-dependent models of hypertensive nephrosclerosis and is temporally and spatially related to M Phi infiltration. The angiotensin II type 1 receptor mediates the induction of MCP-1.