Renin-angiotensin system and fibronectin gene expression in Dahl Iwai salt-sensitive and salt-resistant rats

Objective The tissue renin-angiotensin system and extracellular matrix are involved in the cardiovascular hypertrophy and remodeling induced by hypert ension. In this study, we examined the gene expression of the tissue renin- angiotensin system and fibronectin in inbred Dahl Iwai salt-sensitive and s alt-resistant rats. Materials and methods Eight pairs of 6-week-old male Dahl Iwai salt-sensiti ve and salt-resistant rats were fed either a low- or high-salt diet (0.3% o r 8% NaCl, respectively) for 4 weeks. Activities of the circulating renin-a ngiotensin system were measured by radioimmunoassay and the gene expression of tissue angiotensinogen, the angiotensin II type 1 receptor(AT(1)) and f ibronectin were analyzed by Northern blot analysis. Results Salt loading significantly increased blood pressure and produced ca rdiovascular hypertrophy and nephrosclerosis in the salt-sensitive rats. Ac tivities of the circulating renin-angiotensin system were lower in salt-sen sitive rats than in salt-resistant rats fed the low-salt diet, and salt loa ding lowered these activities in salt-resistant rats but not in salt-sensit ive rats. In salt-resistant rats, salt loading increased renal, cardiac and aortic angiotensinogen, AT(1) and fibronectin messenger (m)RNA expression except for aortic fibronectin mRNA expression. In contrast, in the salt-sen sitive rats, salt loading stimulated the expression of cardiac fibronectin and aortic angiotensinogen, AT(1) and fibronectin mRNAs. Furthermore, the c ardiac and aortic fibronectin mRNA levels in salt-sensitive rats were highe r than those in salt-resistant rats when both strains were fed the high-sal t diet. Conclusions These results demonstrate that the expression of tissue angiote nsinogen, AT1 and fibronectin mRNAs is regulated differently in Dahl Iwai s alt-sensitive and salt-resistant rats, and indicate that salt-mediated hype rtension activates the cardiac fibronectin gene independently of the tissue renin-angiotensin system and stimulates the aortic fibronectin gene with a ctivation of the tissue renin-angiotensin system. J Hypertens 1999, 17:81-8 9 (C) Lippincott Williams & Wilkins.