Role of angiotensin II in renal injury of deoxycorticosterone acetate-salt hypertensive rats.
To investigate the role of angiotensin II (Ang II) in hypertension-induced tissue injury, we gave TCV-116 (1 mg/kg per day PO), a nonpeptide Ang II type I receptor antagonist, or enalapril (10 mg/kg per day PO) to deoxycorticosterone acetate (DOCA)-salt hypertensive rats for 3 weeks and examined the effects on tissue mRNA levels for transforming growth factor-beta 1 (TGF-beta 1) and extracellular matrix components. Tissue mRNA levels were measured by Northern blot analysis. Renal mRNA levels for TGF-beta 1; types I, III, and IV collagen; and fibronectin in DOCA-salt hypertensive rats were increased by severalfold (P < .01) compared with sham-operated rats. In the aorta of DOCA-salt hypertensive rats, TGF-beta 1 and fibronectin mRNA levels were increased, but types I, III, and IV collagen mRNAs did not increase. In the heart, increased mRNA was found only for fibronectin. Thus, these gene expressions are regulated in a tissue-specific manner. TCV-116 or enalapril did not lower blood pressure in DOCA-salt hypertensive rats. However, the increase in renal mRNAs for TGF-beta 1 and extracellular matrix components in DOCA-salt hypertensive rats was significantly inhibited by treatment with TCV-116 or enalapril, which was associated with a significant decrease in urinary protein and albumin excretions and histological improvement of renal lesions. In contrast, in the aorta and heart these gene expressions were not affected by TCV-116 or enalapril. Thus, local Ang II may contribute to renal injury of DOCA-salt hypertension by stimulating the gene expression of TGF-beta 1 and extracellular matrix components.
Department of Pharmacology, Osaka City University Medical School, Japan.
S
S
Kim
K
K
Ohta
A
A
Hamaguchi
T
T
Omura
T
T
Yukimura
K
K
Miura
Y
Y
Inada
T
T
Wada
Y
Y
Ishimura
F
F
Chatani
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D003094:Collagen / Q000235:genetics; D003900:Desoxycorticosterone; D004656:Enalapril / Q000494:pharmacology; D006973:Hypertension / Q000150:complications* / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood / Q000235:genetics; D012965:Sodium Chloride; D013777:Tetrazoles; D016212:Transforming Growth Factor beta / Q000235:genetics
D001562:Benzimidazoles; D001713:Biphenyl Compounds; D012333:RNA, Messenger; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D004656:Enalapril; D003094:Collagen; D012083:Renin; C077793:candesartan cilexetil