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 hypertension. In this study, we examined the gene expression of the tissue renin-angiotensin system and fibronectin in inbred Dahl Iwai salt-sensitive and salt-resistant rats.


METHODS
Eight pairs of 6-week-old male Dahl Iwai salt-sensitive and salt-resistant rats were fed either a low- or high-salt diet (0.3% or 8% NaCl, respectively) for 4 weeks. Activities of the circulating renin-angiotensin system were measured by radioimmunoassay and the gene expression of tissue angiotensinogen, the angiotensin II type 1 receptor (AT1) and fibronectin were analyzed by Northern blot analysis.


RESULTS
Salt loading significantly increased blood pressure and produced cardiovascular hypertrophy and nephrosclerosis in the salt-sensitive rats. Activities of the circulating renin-angiotensin system were lower in salt-sensitive rats than in salt-resistant rats fed the low-salt diet, and salt loading lowered these activities in salt-resistant rats but not in salt-sensitive rats. In salt-resistant rats, salt loading increased renal, cardiac and aortic angiotensinogen, AT1 and fibronectin messenger (m)RNA expression except for aortic fibronectin mRNA expression. In contrast, in the salt-sensitive rats, salt loading stimulated the expression of cardiac fibronectin and aortic angiotensinogen, AT1 and fibronectin mRNAs. Furthermore, the cardiac and aortic fibronectin mRNA levels in salt-sensitive rats were higher than those in salt-resistant rats when both strains were fed the high-salt diet.


CONCLUSIONS
These results demonstrate that the expression of tissue angiotensinogen, AT1 and fibronectin mRNAs is regulated differently in Dahl Iwai salt-sensitive and salt-resistant rats, and indicate that salt-mediated hypertension activates the cardiac fibronectin gene independently of the tissue renin-angiotensin system and stimulates the aortic fibronectin gene with activation of the tissue renin-angiotensin system.
Tamura
K
K
Department of Internal Medicine II, Yokohama City University School of Medicine, Japan. tamukou@yellow.med.yokohama-cu.ac.jp
Chiba
E
E
Yokoyama
N
N
Sumida
Y
Y
Yabana
M
M
Tamura
N
N
Takasaki
I
I
Takagi
N
N
Ishii
M
M
Horiuchi
M
M
Umemura
S
S
D000803:Angiotensin I / Q000235:genetics; D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D001794:Blood Pressure; D015152:Blotting, Northern; D005353:Fibronectins / Q000235:genetics*; D015870:Gene Expression; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis*; D011863:Radioimmunoassay; D051381:Rats; D020303:Rats, Inbred Dahl; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*; D012982:Sodium, Dietary / Q000008:administration & dosage*
D005353:Fibronectins; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D012982:Sodium, Dietary; D000808:Angiotensinogen; D000803:Angiotensin I