ROLE OF ANGIOTENSIN-II IN RENAL INJURY OF DEOXYCORTICOSTERONE ACETATESALT HYPERTENSIVE RATS

To investigate the role of angiotensin II (Ang II) in hypertension-ind uced 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 we eks and examined the effects on tissue mRNA levels for transforming gr owth factor-beta 1 (TOP-beta 1) and extracellular matrix components. T issue mRNA levels were measured by Northern blot analysis. Penal 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) c ompared with sham-operated rats. In the aorta of DOCA-salt hypertensiv e rats, TOP-beta 1 and fibronectin mRNA levels were increased, but typ es I, III, and IV collagen mRNAs did not increase. In the heart, incre ased mRNA was found only for fibronectin. Thus, these gene expressions are regulated in a tissue-specific manner. TCV-116 or enalapril did n ot lower blood pressure in DOCA-salt hypertensive rats. However, the i ncrease in renal mRNAs for TGF-beta 1 and extracellular matrix compone nts in DOCA-salt hypertensive rats was significantly inhibited by trea tment with TCV-116 or enalapril, which was associated with a significa nt decrease in urinary protein and albumin excretions and histological improvement of renal lesions. In contrast, in the aorta and heart the se gene expressions were not affected by TCV-116 or enalapril. Thus, l ocal Ang II may contribute to renal injury of DOCA-salt hypertension b y stimulating the gene expression of TGF-beta 1 and extracellular matr ix components.