Role of connective tissue growth factor in vascular and renal damage associated with hypertension in rats. Interactions with angiotensin II.
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. Candesartan-treated 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 expression 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.
de las Heras
Natalia
N
Department of Physiology, School of Medicine, Universidad Complutense, Madrid 28040, Spain.
Ruiz-Ortega
Marta
M
Rupérez
Mónica
M
Sanz-Rosa
David
D
Miana
María
M
Aragoncillo
Paloma
P
Mezzano
Sergio
S
Lahera
Vicente
V
Egido
Jesus
J
Cachofeiro
Victoria
V
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000473:pathology / Q000503:physiopathology*; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D055513:Connective Tissue Growth Factor; D005355:Fibrosis / Q000473:pathology; D006973:Hypertension / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D017874:Immediate-Early Proteins / Q000378:metabolism / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D007668:Kidney / Q000473:pathology / Q000503:physiopathology*; D007672:Kidney Cortex / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
C526316:CCN2 protein, rat; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D000804:Angiotensin II; D055513:Connective Tissue Growth Factor