Increased dietary NaCl potentiates the effects of elevated prorenin levels on blood pressure and organ disease.
BACKGROUND
Rats with several 100-fold elevation of plasma prorenin levels due to liver-specific expression of a rat prorenin transgene have cardiac and aortic hypertrophy, renal lesions, and myocardial fibrosis. The effect of increased dietary NaCl on the phenotype of prorenin transgenic rats has not been examined.


RESULTS
We compared the effects of 0.3 and 2% dietary NaCl in wild-type and transgenic rats from 3 to 12 months of age. In comparison with wild-type rats, transgenic rats receiving 0.3% dietary NaCl had approximately 1000-fold elevation of prorenin, 1.5-fold to 2.5-fold elevation of renin concentration and activity, wild-type levels of angiotensin II, and were hypertensive with cardiac and aortic hypertrophy, and increased renal glomerular and tubulo-interstitial injury score. In wild-type rats, 2% dietary NaCl reduced angiotensin levels, produced a delayed increase in blood pressure, and caused cardiac hypertrophy and tubulo-interstitial injury. By contrast, 2% NaCl did not reduce angiotensin levels in transgenic rats, potentiated their hypertension, cardiac and aortic hypertrophy, and increased myocardial interstitial and perivascular fibrosis, without effect on glomerular or tubulo-interstitial injury score.


CONCLUSIONS
Increased dietary NaCl had a greater impact on the phenotype of transgenic than wild-type rats that may have been due, in part, to their hypertension and their failure to suppress angiotensin levels, consequent to their elevated prorenin levels.
Campbell
Duncan J
DJ
St. Vincent's Institute of Medical Research, and Department of Medicine, University of Melbourne, St. Vincent's Hospital, Fitzroy, Victoria, Australia. dcampbell@svi.edu.au
Karam
Habib
H
Bruneval
Patrick
P
Mullins
John J
JJ
Ménard
Joël
J
D000804:Angiotensin II / Q000378:metabolism; D000809:Angiotensins / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology; D012085:Chymosin; D004792:Enzyme Precursors / Q000235:genetics; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D006973:Hypertension / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology*; D008297:Male; D011897:Random Allocation; D051381:Rats; D055647:Rats, Transgenic; D012083:Renin / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*
D000809:Angiotensins; D004792:Enzyme Precursors; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II; C032443:prorennin; D012083:Renin; D012085:Chymosin
Mol Cell Endocrinol. 2009 Apr 29;302(2):213-8
18840499
J Clin Invest. 2002 Jun;109(11):1417-27
12045255
Physiol Res. 2004;53(6):581-93
15588125
Kidney Int. 1986 Apr;29(4):849-57
3712968
Am J Physiol Heart Circ Physiol. 2008 Sep;295(3):H1117-H1121
18621861
Hypertension. 1993 Sep;22(3):339-47
8349327
Hypertension. 1998 Aug;32(2):273-9
9719054
Am J Physiol. 1996 Oct;271(4 Pt 2):F824-30
8898012
Endocrinology. 1994 Jan;134(1):253-7
8275941
Hypertension. 2008 May;51(5):1259-64
18347225
Hypertension. 1995 May;25(5):1014-20
7737708
Clin Exp Hypertens A. 1987;9(8-9):1353-66
2820626
J Hypertens. 1991 Mar;9(3):265-74
1851790
Hypertension. 2009 Dec;54(6):1248-53
19841286
Circulation. 1998 Dec 8;98(23):2621-8
9843472
J Clin Invest. 1983 Dec;72(6):2115-24
6358261
J Hypertens. 2006 Jun;24(6):1147-55
16685215
Hypertension. 2001 Feb;37(2):255-60
11230281
Kidney Int. 1984 Aug;26(2):137-43
6239058
J Clin Invest. 1996 Nov 1;98(9):1966-70
8903314