title: Reduction of renal immune cell infiltration results in blood pressure control in genetically hypertensive rats.
abstract: 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.
authors.affiliation: Renal Service and Laboratory, Hospital Universitario, Instituto de Investigaciones Biomédicas, Universidad del Zulia, Maracaibo, Zulia 4001-A, Venezuela.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Rodríguez-Iturbe
authors.forename: Yasmir
authors.initials: Y
authors.lastname: Quiroz
authors.forename: Mayerly
authors.initials: M
authors.lastname: Nava
authors.forename: Lizzette
authors.initials: L
authors.lastname: Bonet
authors.forename: Maribel
authors.initials: M
authors.lastname: Chávez
authors.forename: Jaime
authors.initials: J
authors.lastname: Herrera-Acosta
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
authors.forename: Héctor A
authors.initials: HA
authors.lastname: Pons
mesh_terms: 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
chemical_list: D007166:Immunosuppressive Agents; D013481:Superoxides; D000804:Angiotensin II; D008315:Malondialdehyde; D002374:Catalase; D005978:Glutathione; D009173:Mycophenolic Acid