title: Effect of aging and hypertension on myosin biochemistry and gene expression in the rat heart.
abstract: 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.
authors.affiliation: Department of Medicine, Montefiore Medical Center, Bronx, N.Y. 10467.
authors.forename: P
authors.initials: P
authors.lastname: Buttrick
authors.forename: A
authors.initials: A
authors.lastname: Malhotra
authors.forename: S
authors.initials: S
authors.lastname: Factor
authors.forename: D
authors.initials: D
authors.lastname: Greenen
authors.forename: L
authors.initials: L
authors.lastname: Leinwand
authors.forename: J
authors.initials: J
authors.lastname: Scheuer
mesh_terms: 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
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; D013963:Thyroid Hormones; D009218:Myosins