Tian N, Gu JW, Jordan S, Rose RA, Hughson MD, Manning RD Jr. Immune suppression prevents renal damage and dysfunction and reduces arterial pressure in salt-sensitive hypertension. Am J Physiol Heart Circ Physiol 292: H1018 -H1025, 2007. First published October 13, 2006; doi:10.1152/ajpheart.00487.2006.-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 ϩ MMF (20 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ), 0.3% Na, or 0.3% Na ϩ 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 ϩ 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 Ϯ 5 mmHg, and MMF reduced this arterial pressure to 124 Ϯ 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 SEVERAL MECHANISMS have been found to contribute to the etiology of salt-sensitive hypertension, including reduced levels of NO (7) and elevated oxidative stress (12,29). In addition to these factors, there is emerging evidence indicating that the immune system may play an important role in salt-sensitive hypertension.In several models of hypertension, renal tubulointerstitial infiltration of macrophages and lymphocytes occurs. Renal immunocompetent cells have been found in DOCA hypertension (27), post-angiotensin II (ANG) salt-sensitive hypertension (21), hypertension following NO inhibition (20), protein overload nephropathy (1), the spontaneously hypertensive rate (SHR) (22) and the double-transgenic rat (dTGR) that has human renin and angiotensinogen genes (18). Anti-immune therapy administered to each of the above models of hypertension successfully decreased arterial pressure (24).Dahl salt-sensitive hypertension is characterized by increases in oxidative stress, severe renal damage, and decreases in renal hemodynamics (29); however, the role of renal immune cell infil...

In Dahl S rats on high sodium intake, arterial pressure increases significantly and renal injury is pronounced. Treatment with N-acetylcysteine enhances the renal glutathione system, improves renal dysfunction and markedly decreases arterial pressure and renal injury in Dahl salt-sensitive hypertension.