Immune suppression blocks sodium-sensitive hypertension following recovery from ischemic acute renal failure.
The present study determined the effect of immune suppression with mycophenolate mofetil (MMF) on sodium-sensitive hypertension following recovery from ischemia reperfusion (I/R)-induced acute renal failure. Male Sprague-Dawley rats fed 0.4% NaCl chow were subjected to 40 min bilateral I/R or control sham surgery. After 35 days of recovery, when plasma creatinine levels had returned to normal, the rats were switched to 4.0% NaCl chow for 28 days and administered vehicle or MMF (20 mg.kg(-1).day(-1) ip). High-salt mean arterial pressure was significantly higher in I/R rats (144 +/- 16 mmHg) compared with vehicle-treated sham rats (122 +/- 2 mmHg). Treatment of I/R rats with MMF during the period of high salt intake prevented the salt-induced increase in arterial pressure (114 +/- 3 mmHg). Conscious creatinine clearance was lower in I/R rats (0.27 +/- 0.07 ml.min(-1).100 g body wt(-1)) compared with vehicle-treated sham rats (0.58 +/- 0.04 ml.min(-1).100 g body wt(-1)); MMF treatment prevented the decrease in creatinine clearance in I/R rats (0.64 +/- 0.07 ml.min(-1).100 g body wt(-1)). I/R injury also significantly increased glomerular tissue damage and increased the presence of ED-1 positive (macrophages) and S100A4 positive cells (fibroblasts) in the renal interstitium. The I/R rats treated with MMF exhibited a significant reduction in infiltrating macrophages and fibroblasts and decreased histological damage. The present data indicate that infiltrating immune cells mediate or participate in the development of sodium-sensitive hypertension and renal damage in rats apparently recovered from renal I/R injury.
Pechman
Kimberly R
KR
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Basile
David P
DP
Lund
Hayley
H
Mattson
David L
DL
D058186:Acute Kidney Injury / Q000150:complications* / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007511:Ischemia / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000601:surgery; D008264:Macrophages / Q000187:drug effects; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications* / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D017673:Sodium Chloride, Dietary; D013997:Time Factors
D007166:Immunosuppressive Agents; D017673:Sodium Chloride, Dietary; D003404:Creatinine; D009173:Mycophenolic Acid