Angiotensin converting enzyme inhibition in Dahl salt-sensitive rats.
Angiotensin II has previously been reported to have in vivo and in vitro cardiac hypertrophic effects. We used the salt-sensitive Dahl rat genetic strain to separate mechanical (pressure overload) vs. hormonal (renin-angiotensin system) input in cardiac hypertrophy. Blood pressure was significantly increased and left ventricular hypertrophy, as indexed by LV/BW ratios, was present at 7 and 15 days in rats receiving 4% and 8% NaCl compared to the 1% controls. There was no effect of the angiotensin converting enzyme inhibitor, enalapril maleate, on lowering the blood pressure in 8% NaCl-treated animals, however, there was a significant reduction in LV/BW ratio in 8% NaCl-treated animals that received this drug. Left ventricular angiotensinogen mRNA activity was significantly reduced in rats receiving 4% and 8% NaCl. In this model of hypertension the cardiac hypertrophy which develops is largely dependent on mechanical forces though there remains a significant contribution to this process from either circulating or localized angiotensin II production. Regulation of angiotensinogen gene expression in the hypertrophied left ventricle suggests that volume and electrolyte control of angiotensinogen gene expression in the heart and/or hereditary factors are predominant in the control of regulation of this gene in the left ventricle of Dahl rats.
Peeler
T C
TC
Weis Center for Research, Danville, PA 17822.
Baker
K M
KM
Esmurdoc
C F
CF
Chernin
M I
MI
D000704:Analysis of Variance; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D004656:Enalapril / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D051381:Rats; D012084:Renin-Angiotensin System / Q000502:physiology; D012965:Sodium Chloride / Q000494:pharmacology
D000804:Angiotensin II; D012965:Sodium Chloride; D012313:RNA; D004656:Enalapril