Effects of Renin-Angiotensin System Blockade on Macrophage Infiltration in Patients with Hypertensive Nephrosclerosis

• Published in: Hypertension research Vol. 30; no. 7; pp. 635 - 642
• Main Authors: Imakiire, Toshihiko, Kikuchi, Yuichi, Yamada, Muneharu, Kushiyama, Taketoshi, Higashi, Keishi, Hyodo, Naomi, Yamamoto, Kojiro, Oda, Takashi, Suzuki, Shigenobu, Miura, Soichiro
• Format: Journal Article
• Language: English
• Published: England 01.07.2007
• Subjects: Adolescent; Adult; Aged; Angiotensin II Type 1 Receptor Blockers - pharmacology; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Biopsy; Cell Movement - drug effects; Cell Movement - physiology; Chemokine CCL2 - metabolism; Glomerulonephritis, IGA - etiology; Glomerulonephritis, IGA - pathology; Glomerulonephritis, IGA - physiopathology; Glomerulonephritis, Membranous - etiology; Glomerulonephritis, Membranous - pathology; Glomerulonephritis, Membranous - physiopathology; Humans; Hypertension - complications; Hypertension - physiopathology; Kidney Glomerulus - metabolism; Kidney Glomerulus - pathology; Kidney Glomerulus - physiopathology; Macrophages - drug effects; Macrophages - pathology; Middle Aged; Nephrosclerosis - etiology; Nephrosclerosis - pathology; Nephrosclerosis - physiopathology; Nephrosis, Lipoid - etiology; Nephrosis, Lipoid - pathology; Nephrosis, Lipoid - physiopathology; Renin-Angiotensin System - drug effects; Renin-Angiotensin System - physiology; Retrospective Studies
• ISSN: 0916-9636; 1348-4214
• DOI: 10.1291/hypres.30.635

The mechanisms of hypertensive nephrosclerosis are not fully understood. In experimental models of the disease, inflammatory reactions such as macrophage infiltration play an important role. In human hypertensive nephrosclerosis, however, there have been few studies examining the role of inflammation histologically. We investigated whether the number of infiltrating macrophages was increased in human hypertensive nephrosclerosis, and evaluated the effects of a blockade of the renin-angiotensin system on clinical and histological findings. We examined macrophage infiltration using immunohistochemistry in renal biopsy specimens obtained from 16 patients with hypertensive nephrosclerosis, 5 patients with IgA nephropathy, 5 patients with membranous nephropathy, and 5 patients with minimal change nephrotic syndrome. The number of infiltrating macrophages in glomeruli was significantly larger in the patients with hypertensive nephrosclerosis than in those with minimal change nephrotic syndrome. The patients with hypertensive nephrosclerosis were divided into groups based on their use of antihypertensive agents at the time of renal biopsy. We investigated the effects of antihypertensive agents on clinical findings, macrophage infiltration, and monocyte chemoattractant protein-1 expression. There was no difference in clinical findings between the hypertensive groups. The numbers of infiltrating macrophages and monocyte chemoattractant protein-1-positive cells in glomeruli were significantly smaller in patients treated with an angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor blocker, whereas calcium channel blockers had no influence on histological findings. In conclusion, inflammation is involved in the progression of human hypertensive nephrosclerosis and the inflammatory process is inhibited by blocking the renin-angiotensin system.