Interactions between aldosterone and connective tissue growth factor in vascular and renal damage in spontaneously hypertensive rats

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. Method Spontaneously hypertensive rats (SHR) were treated with two doses (1100 and 30 mg/kg per day) of mineralocorticoid receptor antagonist eplerenone, or with anti hypertensive therapy (HHR) (20mg/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 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 (1100 mg/kg per day). The direct effect of aldosterone on vascular smooth muscle cells was also studied. of cultured vascular smooth muscle cells with 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.