Papel del factor de crecimiento de tejido conectivo en el daño vascular asociado a hipertensión en ratas. Interacción con la aldosterona
- Natalia de Las Heras 1
- Marta Ruiz-Ortega 2
- María Miana 1
- Mónica Rupérez 2
- David Sanz-Rosa 1
- Paloma Aragoncillo 3
- Sergio Mezzano 4
- Victoria Cachofeiro 1
- Jesús Egido 2
- Vicente Lahera 1
- 1 Departamento de Fisiología. Facultad de Medicina. Universidad Complutense. Madrid
- 2 Laboratorio de Investigación Renal y Vascular. Fundación Jiménez Díaz
- 3 Departamento de Patología. Unidad II. Hospital Clínico San Carlos. Madrid
- 4 División de Nefrología. Facultad de Medicina. Universidad Austral. Valdivia. Chile
ISSN: 0214-9168, 1578-1879
Year of publication: 2007
Volume: 19
Issue: 5
Pages: 232-239
Type: Article
More publications in: Clínica e investigación en arteriosclerosis
Abstract
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.