title: Participation of aldosterone in the vascular inflammatory response of spontaneously hypertensive rats: role of the NFkappaB/IkappaB system.
abstract: OBJECTIVE
  To investigate the participation of aldosterone in the vascular inflammatory process associated with hypertension, as well as the possible involvement of the NFkappaB/IkappaB system.
  
  
  METHODS
  Male spontaneously hypertensive rats (SHR; 20-22 weeks old) untreated or treated with either the aldosterone receptor antagonist, eplerenone (100 mg/kg per day) or triple antihypertensive therapy (HHR: hydralazine + hydrochlorothiazide + reserpine; 20 + 7 + 0.15 mg/kg per day) were used in the study. Wistar-Kyoto rats (WKY) were used as a normotensive reference group. Aortic mRNA expression and plasma levels of interleukin (IL)-1beta, IL-6 and tumour necrosis factor alpha (TNFalpha) were measured. Likewise, the aortic expression of the nuclear factor kappaB (NFkappaB) p50 subunit precursor, p105, and its inhibitor (IkappaB) were measured.
  
  
  RESULTS
  SHR showed higher aortic expression of IL-1beta, IL-6 and TNFalpha than WKY (P < 0.05) and higher plasma levels of IL-1beta and IL-6 than WKY (P < 0.05). Moreover, SHR also presented increased aortic expression of nuclear transcription factor NFkappaB p50 subunit precursor (p105), and a reduction of its inhibitor IkappaB. Both eplerenone and HHR decreased blood pressure to a comparable extent (P < 0.05). This effect was accompanied by a reduction in plasma levels of IL-1beta and IL-6 and aortic mRNA expression of IL-1beta, IL-6 and TNFalpha. However, the effect of eplerenone was more marked, since eplerenone-treated rats showed significantly lower inflammatory parameters than SHR receiving HHR. In addition, both antihypertensive treatments increased IkappaB mRNA expression in a similar manner, but only eplerenone reduced NFkappaB mRNA expression.
  
  
  CONCLUSIONS
  Aldosterone, as well as an increase in haemodynamic forces produced by hypertension, participate in the vascular inflammatory process associated with hypertension in SHR. This effect seems to be mediated by enhanced vascular expression of cytokines through a modification of the NFkappaB/IkappaB system.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Sanz-Rosa
authors.forename: Eva
authors.initials: E
authors.lastname: Cediel
authors.forename: Natalia
authors.initials: N
authors.lastname: de las Heras
authors.forename: Maria
authors.initials: M
authors.lastname: Miana
authors.forename: Gloria
authors.initials: G
authors.lastname: Balfagón
authors.forename: Vicente
authors.initials: V
authors.lastname: Lahera
authors.forename: Victoria
authors.initials: V
authors.lastname: Cachofeiro
mesh_terms: D000450:Aldosterone / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D004359:Drug Therapy, Combination; D000077545:Eplerenone; D006973:Hypertension / Q000188:drug therapy / Q000276:immunology*; D020672:I-kappa B Proteins / Q000378:metabolism*; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014657:Vasculitis / Q000188:drug therapy / Q000276:immunology*
chemical_list: D000959:Antihypertensive Agents; D020672:I-kappa B Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D000451:Mineralocorticoid Receptor Antagonists; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone