title: Immune regulation and vascular inflammation in genetic hypertension.
abstract: Immune cells have been implicated in the pathogenesis of hypertension. We hypothesized that under the influence of chromosome (chr)2, T lymphocytes contribute to vascular inflammation in genetic salt-sensitive hypertension. Normotensive (Brown Norway), hypertensive (Dahl salt-sensitive), and consomic rats (SSBN2; in which chr2 has been transferred from Brown Norway to Dahl rats) were studied. Systolic blood pressure, measured by tail cuff, and aortic preproendothelin mRNA, measured by quantitative RT-PCR, were elevated in Dahl rats compared with Brown Norway rats and were reduced in SSBN2 rats compared with Dahl rats (P < 0.01). Compared with Brown Norway rats, Dahl rats exhibited increased inflammatory markers and mediators such as nuclear translocation of the aortic p65 subunit of NF-kappaB as well as VCAM-1, ICAM-1, chemokine (C-C motif) receptor 5, and CD4 mRNA, all of which were reduced in SSBN2 rats. Aortic CD8 mRNA was equally increased in Dahl and SSBN2 rats relative to Brown Norway rats. CD4(+) T cell infiltration in the aorta of SSBN2 rats was reduced compared with Dahl rats, whereas the aortic protein expression of Foxp3b and immunosuppressors transforming growth factor (TGF)-beta(1) and IL-10, the three markers associated with the regulatory T cell lineage, were enhanced in SSBN2 rats. Activation in vitro of T cells demonstrated that CD4(+)CD25(+) and CD8(+)CD25(+) cells (Tregs) produce IL-10 in SSBN2 rats. Thus, increased vascular inflammatory responses and hypertension in a genetic salt-sensitive hypertensive rodent model are reduced by transfer of chr2 from a normotensive strain, and this is associated with enhanced levels of immunosuppressive mediators.
authors.affiliation: Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
authors.forename: Emilie C
authors.initials: EC
authors.lastname: Viel
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Lemarié
authors.forename: Karim
authors.initials: K
authors.lastname: Benkirane
authors.forename: Pierre
authors.initials: P
authors.lastname: Paradis
authors.forename: Ernesto L
authors.initials: EL
authors.lastname: Schiffrin
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure / Q000502:physiology*; D002452:Cell Count; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology*; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D020303:Rats, Inbred Dahl; D011919:Rats, Inbred Strains; D050378:T-Lymphocytes, Regulatory / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014657:Vasculitis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
chemical_list: D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10