Effect of aging and hypertension on myosin biochemistry and gene expression in the rat heart.
The mechanisms by which the aged heart adapts to a superimposed pressure load such as hypertension have not been described. We therefore investigated biochemical and molecular genetic adaptations in the 24-month-old rat heart subjected to renovascular hypertension. Compared with 4-month-old rats, aging was associated with a 68% increase in left ventricular mass without any change in heart weight-to-body weight ratio, a 33% reduction in calcium-activated myosin ATPase activity, and a shift from a V1 to a V3 predominant myosin heavy chain (MHC) isoform distribution. A 46% reduction in alpha-MHC mRNA and a reciprocal increase in beta-MHC mRNA was seen. When hypertension was superimposed, there was a further 75% increase in ventricular mass, a 63% increase in heart weight-to-body weight ratio, and a 19% reduction in myosin ATPase. Myosin isozyme distribution was further shifted to V3, and the ratio of alpha-MHC to beta-MHC mRNA was reduced. In addition, with hypertension a significant (greater than 50%) reduction in the mRNA level of the cardiac sarcoplasmic reticular calcium-activated ATPase was seen. These data demonstrate that the aged myocardium is able to respond to a superimposed pressure load with a molecular genetic and protein synthetic pattern of hypertrophy analogous to that seen in younger animals.
Buttrick
P
P
Department of Medicine, Montefiore Medical Center, Bronx, N.Y. 10467.
Malhotra
A
A
Factor
S
S
Greenen
D
D
Leinwand
L
L
Scheuer
J
J
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D015870:Gene Expression; D006321:Heart / Q000502:physiology*; D006973:Hypertension / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D009218:Myosins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013963:Thyroid Hormones / Q000097:blood
D007527:Isoenzymes; D012333:RNA, Messenger; D013963:Thyroid Hormones; D009218:Myosins