Regression of cardiac hypertrophy in spontaneously hypertensive rats by enalapril and the expression of contractile proteins.
Several experimental models involving the development of cardiac hypertrophy in adult rats are characterized by the reexpression of the fetal isoform of myosin heavy chain (V3). To determine whether a similar adult-to-fetal shift in the expression of the thin-filament proteins occurs during cardiac hypertrophy, we have examined the expression of the isoforms of myosin, tropomyosin, and troponin T in the left ventricle of young spontaneously hypertensive rats (SHR) with and without treatment using enalapril, an angiotensin converting enzyme inhibitor. Phosphorylation of tropomyosin, which is predominant in the fetal state, was also analyzed. Twelve-week-old SHR were treated with enalapril for 2, 5, 8, and 9 weeks followed by withdrawal of treatment for 9 weeks. Control SHR, without drug treatment, were weight- and age-matched. After 9 weeks of enalapril treatment, mean arterial blood pressure was reduced (from 166 +/- 11 to 89 +/- 5 mm Hg), and left ventricular weight/body weight ratio was regressed (from 2.53 +/- 0.14 to 1.96 +/- 0.05 g/kg) to normotensive levels. During the 9-week treatment period, the percent V3 decreased in SHR substantially from 35 +/- 3% to 13 +/- 1%. There was a significant correlation between the left ventricular hypertrophy and the percent V3 myosin expression in the SHR during regression (r = 0.697, p less than 0.001). However, only the adult isoforms of tropomyosin and troponin T were detected in the SHR with or without enalapril treatment, and the level of tropomyosin phosphorylation remained constant irrespective of the degree of left ventricular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
Childs
T J
TJ
Department of Biochemistry, Queen's University, Kingston, Ontario, Canada.
Adams
M A
MA
Mak
A S
AS
D000818:Animals; D001794:Blood Pressure; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D003285:Contractile Proteins / Q000378:metabolism*; D004656:Enalapril / Q000494:pharmacology*; D006352:Heart Ventricles; D007527:Isoenzymes / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D014335:Tropomyosin / Q000378:metabolism; D014336:Troponin / Q000378:metabolism; D020107:Troponin T
D003285:Contractile Proteins; D007527:Isoenzymes; D014335:Tropomyosin; D014336:Troponin; D020107:Troponin T; D004656:Enalapril; D009218:Myosins