Does mycophenolate mofetil reduce arterial blood pressure and kidney damage in Dahl salt-sensitive rats fed a high-salt diet?
Infiltrating T lymphocytes mediate salt-sensitive hypertension and kidney damage in Dahl SS rats by participating in the intrarenal production of ANG II, which can be attenuated by immunosuppression with mycophenolate mofetil.
This study examined mechanisms by which immune cells participate in the development of hypertension and renal disease in Dahl salt-sensitive (SS) rats. Increasing dietary salt from 0.4% to 4.0% NaCl significantly increased renal infiltration of T lymphocytes from 8.8 +/- 1.2 x 10(5) to 14.4 +/- 2.0 x 10(5) cells/2 kidneys, increased arterial blood pressure from 131 +/- 2 to 165 +/- 6 mmHg, increased albumin excretion rate from 17 +/- 3 to 129 +/- 20 mg/day, and resulted in renal glomerular and tubular damage. Furthermore, renal tissue ANG II was not suppressed in the kidneys of SS rats fed 4.0% NaCl. Administration of the immunosuppressive agent mycophenolate mofetil (MMF; 20 mg.kg(-1).day(-1)) prevented the infiltration of T lymphocytes and attenuated Dahl SS hypertension and renal disease. In contrast to vehicle-treated rats, Dahl SS rats administered MMF demonstrated a suppression of renal tissue ANG II from 163 +/- 26 to 88 +/- 9 pg/g of tissue when fed high salt. Finally, it was demonstrated that the T lymphocytes isolated from the kidney possess renin and angiotensin-converting enzyme activity. These data indicate that infiltrating T cells are capable of participating in the production of ANG II and are associated with increased intrarenal ANG II, hypertension, and renal disease. The suppression of T-cell infiltration decreased intrarenal ANG II and prevented Dahl SS hypertension and kidney damage. As such, infiltrating cells are capable of participating in the established phase of Dahl SS hypertension.
Miguel et al. (Thu,) studied this question.