期刊
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
卷 282, 期 2, 页码 F191-F201出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.0197.2001
关键词
immune cells; spontaneously hypertensive rats; mycophenolate mofetil; oxidative stress
资金
- NIDDK NIH HHS [DK-47659, DK-52121] Funding Source: Medline
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, Rincon J, Chavez M, Parra G, Herrera-Acosta J, Gomez-Garre D, Largo R, Egido J, Johnson RJ, and Rodriguez-Iturbe B. Am J Physiol Renal Physiol 281: F38-F47, 2001; Rodriguez-Iturbe B, Pons H, Quiroz Y, Gordon K, Rincon J, Chavez M, Parra G, Herrera-Acosta J, Gomez-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).day(-1) 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.
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