Immune Suppression Prevents Renal Damage and Dysfunction and Reduces Arterial Pressure in Salt‐Sensitive Hypertension

Abstract

Salt-sensitive hypertension is characterized by progressive increases in proteinuria and renal pathological damage and decreases in renal hemodynamics. Recent studies have shown that activation of the immune system may play an important role in the development of renal injury and hypertension. However, the role of immune system in the Dahl salt-sensitive hypertension is not clear. The Dahl salt-sensitive rat (Dahl S) was used as a model of salt-sensitive hypertension, and in one group the immunosuppressive drug mycophenolate mofetil (MMF) was given during the entire experimental period. Dahl S rats (n= 7–10 in each group) were equipped with arterial and venous catheters and subjected to a 5-week diet of high Na (8% NaCl), low Na (0.3% NaCl) or high Na + MMF. Mean arterial pressure (MAP) was measured continuously throughout the last 10 days. By the end of week 5 in the high Na + MMF group: mean arterial pressure was 124 ± 3 mmHg compared to the high Na group value of 182 ± 5 mmHg†; GFR, effective renal plasma flow and urinary protein excretion, an index of renal damage, were 3.9 ± 0.2 ml/min, 14 ± 0.7 ml/min, 52 ± 10 mg/day compared to the high Na group values of 2.3 ± 0.2 ml/min†, 7.7 ± 0.8 ml/min† and 114 ± 16 mg/day†, respectively. In summary, long term MMF treatment in Dahl S rats with high Na intake decreased mean arterial pressure and urinary protein excretion and markedly increased GFR and renal plasma flow. Immune activation plays an important role in Dahl salt-sensitive hypertension by increasing arterial pressure and renal damage and decreasing renal hemodynamics. Support: NIH grant HL51971.