Prevention of high salt diet-induced cardiac hypertrophy and fibrosis by spironolactone.
BACKGROUND
High salt diet causes cardiac hypertrophy and fibrosis and increases cardiac aldosterone, while decreasing plasma aldosterone. The present study assessed, in Wistar rats, the effect of high salt diet on left and right ventricle (LV and RV, respectively) weight and fibrosis both with and without the aldosterone antagonist spironolactone.


METHODS
Regular salt (0.6%) or high salt (8%) diet either without or with spironolactone (20 or 80 mg/kg/day) were given to Wistar rats for 4 and 8 weeks.


RESULTS
A modest increase in BP was noted only after 8 weeks on high salt diet. Both LV weight and cardiomyocyte cross-sectional diameter were increased significantly by high salt diet after 4 and 8 weeks, whereas RV weight remained unchanged. Both LV and RV collagen as well as interstitial and perivascular fibrosis remained unchanged after 4 weeks and increased significantly after 8 weeks on high salt diet. Spironolactone at a dose of 80 mg/kg prevented increases in LV weight and cardiomyocyte cross-sectional diameter, as well as increases in LV and RV collagen and interstitial and perivascular fibrosis induced by high salt diet. In comparison, spironolactone at a dose of 20 mg/kg was somewhat less effective.


CONCLUSIONS
Chronic high salt diet increases LV weight and cardiomyocyte cross-sectional diameter and causes both LV and RV fibrosis. All of these changes are prevented by spironolactone, which is consistent with the concept that cardiac aldosterone mediates these cardiac effects of high salt diet.
Lal
Avtar
A
Hypertension Unit, University of Ottawa Heart Institute, Ontario, Canada.
Veinot
John P
JP
Leenen
Frans H H
FH
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000209:etiology* / Q000517:prevention & control*; D003094:Collagen / Q000378:metabolism; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis; D006321:Heart / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D013148:Spironolactone / Q000008:administration & dosage / Q000494:pharmacology*
D004232:Diuretics; D017673:Sodium Chloride, Dietary; D013148:Spironolactone; D003094:Collagen