Immune suppression attenuates hypertension and renal disease in the Dahl salt-sensitive rat.
Experiments were performed to determine the importance of activation or infiltration of immune cells in the kidney during the development of hypertension and renal disease in Dahl salt-sensitive rats (SS/Mcw) fed a 4.0% NaCl diet. Compared with vehicle-treated rats, chronic administration of mycophenolate mofetil ([MMF] 30 mg/kg per day, IP), an immunosuppressive agent that has cytostatic effects on T and B cells, decreased cell-specific markers of T and B cells by 50% to 60% in the kidneys of SS/Mcw rats (n=5 per group). Further studies were performed on Dahl SS/Mcw rats, which were instrumented with chronic indwelling catheters and studied after 3 weeks on the 4.0% NaCl diet. Rats were administered MMF or 5% dextrose vehicle daily during the 3-week period of high NaCl intake. Mean arterial blood pressure in the rats administered MMF (122+/-2 mm Hg; n=11) was significantly decreased compared with vehicle-treated rats (139+/-4 mm Hg; n=9). Furthermore, the rate of protein (112+/-13 mg per day) and albumin excretion (15+/-3 mg per day) in the MMF-treated rats was significantly lower than the protein and albumin excretion rate in vehicle-treated rats (167+/-25 and 31+/-7 mg per day, respectively). Creatinine clearance and body weight were not different between the groups, averaging 0.52+/-0.08 mL/min per gram kidney weight and 322+/-10 g, respectively, in the MMF-treated group. These experiments indicate that the activation of the immune system or renal infiltration of immune cells plays an important role in the development of hypertension and renal disease in Dahl SS/Mcw rats consuming an elevated NaCl diet.
Mattson
David L
DL
Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. dmattson@mcw.edu
James
Leilani
L
Berdan
Elizabeth A
EA
Meister
Carla J
CJ
D000418:Albumins / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000276:immunology; D003404:Creatinine / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000276:immunology / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011506:Proteins / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D012965:Sodium Chloride / Q000008:administration & dosage
D000418:Albumins; D007166:Immunosuppressive Agents; D011506:Proteins; D012965:Sodium Chloride; D003404:Creatinine; D009173:Mycophenolic Acid