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Role of connective tissue growth factor in vascular and renal damage associated with hypertension in rats. Interactions with angiotensin II
Natalia de las Heras
Department of Physiology, School of Medicine, Universidad Complutense, Madrid, Spain
Marta Ruiz-Ortega
Laboratory of Renal and Vascular Research, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain
Mónica Rupérez
Laboratory of Renal and Vascular Research, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain
David Sanz-Rosa
Department of Physiology, School of Medicine, Universidad Complutense, Madrid, Spain
María Miana
Department of Physiology, School of Medicine, Universidad Complutense, Madrid, Spain
Paloma Aragoncillo
Department of Pathology Unit , Hospital Clínico Universitario San Carlos, Madrid, Spain
Sergio Mezzano
Division of Nephrology, School of Medicine, Universidad Austral, Valdivia, Chile
Vicente Lahera
Department of Physiology, School of Medicine, Universidad Complutense, Madrid, Spain
Jesús Egido
Laboratory of Renal and Vascular Research, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain
Victoria Cachofeiro
Department of Physiology, School of Medicine, Universidad Complutense, Madrid, Spain, vcara{at}med.ucm.es
We have evaluated the role of connective tissue growth factor (CTGF) in vascular and renal damage associated with hypertension and possible interactions with angiotensin II (Ang II). Spontaneously hypertensive rats (SHR) were treated with either the Ang II receptor antagonist candesartan (C;2 mg/Kg-1/day-1) or antihypertensive triple therapy (TT; in mg/Kg-1/day-1 ;20 hydralazine +7 hydrochlorothiazide +0.15 reserpine) for 10 weeks. Wistar Kyoto rats were used as a normotensive control group. Hypertension was associated with an increase in aortic media area, media-to-lumen ratio and collagen density. Kidneys from SHR showed minimum renal alterations. Aorta and renal gene expression and immunostaining of CTGF were higher in SHR. Candesartan decreased arterial pressure, aortic media area, media-to-lumen ratio and collagen density. However, although arterial pressure decrease was comparable for both treatments,TT partially reduced these parameters. Candesartantreated rats showed lower levels of vascular CTGF expression, aortic media area, media-to-lumen ratio and collagen density than TT-treated animals. Treatments improve renal damage and reduce renal gene exp Pression and CTGF immunostaining in SHR in a similar manner.The results show that vascular and renal damage is associated with stimulation of CTGF gene and protein content.These results also might suggest that CTGF could be one downstream mediator of Ang II in hypertension-associated organ damage in SHR.
Key Words: fibrosis vessel kidney angiotensin CTGF
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Journal of Renin-Angiotensin-Aldosterone System, Vol. 7, No. 4,
192-200 (2006)
DOI: 10.3317/jraas.2006.037

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