title: Interactions between aldosterone and connective tissue growth factor in vascular and renal damage in spontaneously hypertensive rats.
abstract: OBJECTIVE
  The aim of the present study was to investigate possible inter-relationships between connective tissue growth factor (CTGF) and aldosterone in vascular and renal damage associated with hypertension.
  
  
  METHODS
  Spontaneously hypertensive rats (SHR) were treated with two doses (100 and 30 mg/kg per day) of the mineralocorticoid receptor antagonist eplerenone, or with antihypertensive therapy (HHR) (20 mg/kg per day hydralazine + 7 mg/kg per day hydrochlorothiazide + 0.15 mg/kg per day reserpine).
  
  
  RESULTS
  CTGF mRNA expression and protein levels in the aorta of SHR were upregulated (P < 0.05) compared with Wistar-Kyoto rats. Both doses of eplerenone similarly and significantly diminished CTGF upregulation, correlated with amelioration of aortic remodelling and endothelium-dependent relaxations. Only high-dose eplerenone and HHR significantly reduced arterial blood pressure. HHR treatment also diminished CTGF overexpression, suggesting a blood-pressure-mediated effect in CTGF regulation. This reduction, however, was lower (P < 0.05) than that produced by eplerenone (100 mg/kg per day). The direct effect of aldosterone on vascular smooth muscle cells was also studied. Incubation of cultured vascular smooth muscle cells with aldosterone increased CTGF production in a dose-related manner, but was reduced (P < 0.05) by the mineralocorticoid receptor antagonist spironolactone. Renal CTGF mRNA and protein levels were higher in SHR than in Wistar-Kyoto rats (P < 0.05), and were similarly diminished by all treatments (P < 0.05).
  
  
  CONCLUSIONS
  These data show that aldosterone and haemodynamic stress from elevated blood pressure levels regulate vascular and renal CTGF in SHR. The results suggest that aldosterone, through CTGF stimulation, could participate in vascular and renal structural alterations associated with hypertension, describing a novel mechanism of aldosterone in hypertensive target organ damage.
authors.affiliation: Department of Physiology, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: de las Heras
authors.forename: Marta
authors.initials: M
authors.lastname: Ruiz-Ortega
authors.forename: María
authors.initials: M
authors.lastname: Miana
authors.forename: Mónica
authors.initials: M
authors.lastname: Rupérez
authors.forename: David
authors.initials: D
authors.lastname: Sanz-Rosa
authors.forename: Paloma
authors.initials: P
authors.lastname: Aragoncillo
authors.forename: Sergio
authors.initials: S
authors.lastname: Mezzano
authors.forename: Victoria
authors.initials: V
authors.lastname: Cachofeiro
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
authors.forename: Vicente
authors.initials: V
authors.lastname: Lahera
mesh_terms: D000450:Aldosterone / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology*; D001794:Blood Pressure / Q000502:physiology*; D001795:Blood Pressure Determination; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor; D000077545:Eplerenone; D006973:Hypertension / Q000150:complications*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: C526316:CCN2 protein, rat; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D000451:Mineralocorticoid Receptor Antagonists; D055513:Connective Tissue Growth Factor; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone