Immune suppression prevents renal damage and dysfunction and reduces arterial pressure in salt-sensitive hypertension

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 292; no. 2; pp. H1018 - H1025
• Main Authors: Tian, N, Gu, J.-W, Jordan, S, Rose, R. A, Hughson, M. D, Manning, R. D., Jr
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.02.2007
• Subjects: Animals; Blood Pressure - drug effects; Disease Models, Animal; Dose-Response Relationship, Drug; Glomerular Filtration Rate - drug effects; Glutathione - metabolism; Heart Rate - drug effects; Hypertension; Hypertension - chemically induced; Hypertension - physiopathology; Hypertension - prevention & control; Immune system; Immunosuppressive Agents - pharmacology; Immunosuppressive Agents - therapeutic use; Kidney - blood supply; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Kidney diseases; Kidney Diseases - chemically induced; Kidney Diseases - pathology; Kidney Diseases - physiopathology; Kidney Diseases - prevention & control; Macrophages - drug effects; Macrophages - pathology; Male; Mycophenolic Acid - analogs & derivatives; Mycophenolic Acid - pharmacology; Mycophenolic Acid - therapeutic use; Nephrology; NF-kappa B - metabolism; Proteinuria - etiology; Proteinuria - prevention & control; Rats; Rats, Inbred Dahl; Renal Circulation - drug effects; Rodents; Sodium Chloride, Dietary; Superoxide Dismutase - metabolism; Superoxides - metabolism; Time Factors; Vascular Resistance - drug effects
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00487.2006

Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi Submitted 12 May 2006 ; accepted in final form 11 October 2006 The goal of this study was to test the hypothesis that renal infiltration of immune cells in Dahl S rats on increased dietary sodium intake contributes to the progression of renal damage, decreases in renal hemodynamics, and development of hypertension. We specifically studied whether anti-immune therapy, using mycophenolate mofetil (MMF), could help prevent increases in renal NF- B activation, renal infiltration of monocytes/macrophages, renal damage, decreases in glomerular filtration rate (GFR) and renal plasma flow, and increases in arterial pressure. Seventy-four 7-to 8-wk-old Dahl S, Rapp strain rats were maintained on an 8% Na, 8% Na + MMF (20 mg·kg –1 ·day –1 ), 0.3% Na, or 0.3% Na + MMF diet for 5 wk. Arterial and venous catheters were implanted at day 21 . By day 35 , renal NF- B in 8% Na rats was 47% higher than in 0.3% Na rats and renal NF- B was 41% lower in 8% Na + MMF rats compared with the 8% Na group. MMF treatment significantly decreased renal monocyte/macrophage infiltration and renal damage and increased GFR and renal plasma flow. In high-NA Dahl S rats mean arterial pressure increased to 182 ± 5 mmHg, and MMF reduced this arterial pressure to 124 ± 3 mmHg. In summary, in Dahl S rats on high sodium intake, treatment with MMF decreases renal NF- B and renal monocyte/macrophage infiltration and improves renal function, lessens renal injury, and decreases arterial pressure. This suggests that renal infiltration of immune cells is associated with increased arterial pressure and renal damage and decreasing GFR and renal plasma flow in Dahl salt-sensitive hypertension. renal failure; macrophages; renal hemodynamics; nuclear factor- B Address for reprint requests and other correspondence: N. Tian, Dept. of Physiology and Biophysics, 2500 North State St., Jackson, MS 39216 (e-mail: ntian{at}physiology.umsmed.edu )