Reduction of renal immune cell infiltration results in blood pressure control in genetically hypertensive rats.
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 x kg(-1) x 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.
Rodríguez-Iturbe
Bernardo
B
Renal Service and Laboratory, Hospital Universitario, Instituto de Investigaciones Biomédicas, Universidad del Zulia, Maracaibo, Zulia 4001-A, Venezuela.
Quiroz
Yasmir
Y
Nava
Mayerly
M
Bonet
Lizzette
L
Chávez
Maribel
M
Herrera-Acosta
Jaime
J
Johnson
Richard J
RJ
Pons
Héctor A
HA
D000804:Angiotensin II / Q000032:analysis; D000818:Animals; D001160:Arterioles / Q000166:cytology; D001794:Blood Pressure / Q000187:drug effects / Q000276:immunology; D002374:Catalase / Q000032:analysis; D005978:Glutathione / Q000032:analysis; D006977:Hypertension, Renal / Q000235:genetics / Q000276:immunology*; D007121:Immunocompetence / Q000502:physiology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000166:cytology / Q000276:immunology; D008214:Lymphocytes / Q000737:chemistry / Q000276:immunology*; D008264:Macrophages / Q000737:chemistry / Q000276:immunology*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013481:Superoxides / Q000032:analysis
D007166:Immunosuppressive Agents; D013481:Superoxides; D000804:Angiotensin II; D008315:Malondialdehyde; D002374:Catalase; D005978:Glutathione; D009173:Mycophenolic Acid