ROLE OF CONNECTIVE TISSUE GROWTH FACTOR IN VASCULAR DAMAGE ASSOCIATED WITH HYPERTENSION IN RATS. INTERACTION WITH ALDOSTERONE

Introduction. Connective tissue growth factor (CTGF) is associated with distinct diseases, including atherosclerosis, skin fibrosis, and several human and experimental nephritides. However, the role of this profibrotic factor in the vascular damage associated with hypertension is not well known. Objective. To study the role of CTGF in vascular alterations associated with hypertension in rats, as well as its possible interaction with aldosterone. Method. Male spontaneously hypertensive rats (SHR) were treated with 2 doses (30 and 100 mg/Kg/day) of the mineralocorticoid receptor antagonist eplerenone for 10 weeks. Normotensive rats (WKY) were used as a control group. At the end of the treatment., systolic blood pressure (SBP) and vascular reactivity in aortic rings were measured. In addition, vascular expression and protein levels of CTGF, as well as morphological lesions in the aorta, were evaluated. The direct effect of aldosterone on vascular smooth muscle cells was also studied. Results. SBP was higher in SHR than in WKY and only the high dose of eplerenone significantly reduced SBP. In the aorta of SHR, CTGF mRNA expression and protein levels were upregulated compared with WKY. Both doses of eplerenone similarly and significantly diminished CTGF upregulation. Endothelium-dependent relaxation was lower in SHR than in WKY and treatment with eplerenone normalized this response. Vessel area, lumen area and media area, as well as the media to lumen ratio, were significantly increased in SHR compared with WKY. 'Treatment with eplerenone reduced all the parameters studied and normalized the media to lumen ratio. Incubation of cultured vascular smooth muscle cells with aldosterone increased CTGF production in a dose-dependent manner Conclusions. Aldosterone participates in both the functional and structural alterations associated with hypertension. CTGF is one of the factors implicated in the vascular fibrotic process associated with hypertension.