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1 Renal Service and Laboratory, Hospital Universitario, Instituto de Investigaciones Biomédicas, Universidad del Zulia, Maracaibo, Zulia 4001-A, Venezuela; 2 Department of Nephrology, Instituto de Cardiología, Mexico City, Tlalpan 14080, Mexico; and 3 Renal Division, Baylor Medical College, Houston, Texas 770030
Immunocompetent cells
infiltrate the kidney in several models of experimental hypertension.
We have previously shown that reduction of this infiltrate results in
prevention of salt-sensitive hypertension induced by short-term
angiotensin II infusion and nitric oxide inhibition (Quiroz Y, Pons H,
Gordon KI, Rincón J, Chávez M, Parra G, Herrera-Acosta J,
Gómez-Garre D, Largo R, Egido J, Johnson RJ, and
Rodríguez-Iturbe B. Am J Physiol Renal Physiol
281: F38-F47, 2001; Rodríguez-Iturbe B, Pons H, Quiroz Y, Gordon K, Rincón J, Chávez M, Parra G,
Herrera-Acosta J, Gómez-Garre D, Largo R, Egido J, and Johnson
RJ. Kidney Int 59: 2222-2232, 2001). We
therefore studied whether hypertension could be controlled in
genetically hypertensive rats [spontaneously hypertensive rats (SHR)]
by the administration of 20 mg · kg
1 · day1 of the
immunosuppressive drug mycophenolate mofetil (MMF group; n = 35). Other SHR received vehicle (n = 35), and Wistar-Kyoto rats (n = 20) were used as
controls. MMF or vehicle was given in two separate 4-wk periods,
separated by a 3-wk interval. Systemic hypertension was reduced to
normal levels in both periods of MMF treatment in association with a
reduction in lymphocyte, macrophage, and angiotensin II-positive cells
infiltrating the kidney. Oxidative stress was also reduced by MMF, as
indicated by a reduction in urinary malondialdehyde (MDA), renal MDA
content, and superoxide-positive cells, and was highly correlated with
blood pressure levels. We conclude that the renal immune infiltrate
plays a major role in the hypertension in SHR.
immune cells; spontaneously hypertensive rats; mycophenolate mofetil; oxidative stress
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