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Role of connective tissue growth factor in vascular and renal damage associated with hypertension in rats. Interactions with angiotensin II

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

Journal of Renin-Angiotensin-Aldosterone System, Vol. 7, No. 4, 192-200 (2006)
DOI: 10.3317/jraas.2006.037


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