title: Increased dietary NaCl potentiates the effects of elevated prorenin levels on blood pressure and organ disease.
abstract: 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.
authors.affiliation: 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
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Campbell
authors.forename: Habib
authors.initials: H
authors.lastname: Karam
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.forename: John J
authors.initials: JJ
authors.lastname: Mullins
authors.forename: Joël
authors.initials: J
authors.lastname: Ménard
mesh_terms: 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*
chemical_list: D000809:Angiotensins; D004792:Enzyme Precursors; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II; C032443:prorennin; D012083:Renin; D012085:Chymosin
references.citation: Mol Cell Endocrinol. 2009 Apr 29;302(2):213-8
references.pmid: 18840499
references.citation: J Clin Invest. 2002 Jun;109(11):1417-27
references.pmid: 12045255
references.citation: Physiol Res. 2004;53(6):581-93
references.pmid: 15588125
references.citation: Kidney Int. 1986 Apr;29(4):849-57
references.pmid: 3712968
references.citation: Am J Physiol Heart Circ Physiol. 2008 Sep;295(3):H1117-H1121
references.pmid: 18621861
references.citation: Hypertension. 1993 Sep;22(3):339-47
references.pmid: 8349327
references.citation: Hypertension. 1998 Aug;32(2):273-9
references.pmid: 9719054
references.citation: Am J Physiol. 1996 Oct;271(4 Pt 2):F824-30
references.pmid: 8898012
references.citation: Endocrinology. 1994 Jan;134(1):253-7
references.pmid: 8275941
references.citation: Hypertension. 2008 May;51(5):1259-64
references.pmid: 18347225
references.citation: Hypertension. 1995 May;25(5):1014-20
references.pmid: 7737708
references.citation: Clin Exp Hypertens A. 1987;9(8-9):1353-66
references.pmid: 2820626
references.citation: J Hypertens. 1991 Mar;9(3):265-74
references.pmid: 1851790
references.citation: Hypertension. 2009 Dec;54(6):1248-53
references.pmid: 19841286
references.citation: Circulation. 1998 Dec 8;98(23):2621-8
references.pmid: 9843472
references.citation: J Clin Invest. 1983 Dec;72(6):2115-24
references.pmid: 6358261
references.citation: J Hypertens. 2006 Jun;24(6):1147-55
references.pmid: 16685215
references.citation: Hypertension. 2001 Feb;37(2):255-60
references.pmid: 11230281
references.citation: Kidney Int. 1984 Aug;26(2):137-43
references.pmid: 6239058
references.citation: J Clin Invest. 1996 Nov 1;98(9):1966-70
references.pmid: 8903314