Protein Synthesis and Amino Acid Transport in the Isolated Rabbit Right Ventricular Papillary Muscle: EFFECT OF ISOMETRIC TENSION DEVELOPMENT

Abstract

To investigate the effects of isometric tension development on myocardial protein metabolism, 14 C-phenylalanine incorporation into protein was studied in the isolated rabbit right ventricular papillary muscle. Amino acid incorporation was linear for 6 hours in resting muscles and was totally inhibited by ICHM cycloheximide and ICHM puromycin. Phenylalanine incorporation into total protein was unaltered by 90 minutes of isometric tension development at peak tension at stimulation rates of 30, 50, or 100/min. Significant increases were noted in muscles stimulated at 50 and 100/min for 180 minutes (P < 0.01). Electrical stimulation, in the absence of isometric tension development, was not responsible for this effect. Passive stretch also appeared to stimulate incorporation, although to a lesser degree than did active tension development. The specific activities of the intracellular phenylalanine pools were identical in control and stimulated muscles. Alpha-aminoisobutyric acid was used to evaluate the effect of tension development on myocardial amino acid transport. Enhanced transport was noted in muscles stimulated isometrically at 30, 50, or 100/min at peak tension. The increased transport ratios could not be solely attributed to active tension development since passive stretch resulted in comparable changes. This study indicates that both passive stretch and tension development are important in regulating myocardial protein synthesis. KEY WORDSpassive stretch mechanochemical coupling alpha-aminoisobutyric acid phenylalanine cardiac work• The heart will hypertrophy when it is exposed to a sustained increase in mechanical work (1-3). This is a positive adaptation which permits the myocardium to meet increased work demands, albeit with a probable decrease in efficiency (4, 5). Alterations in protein and nucleic acid metabolism have been described in many investigations

The influence of activity on muscle size and protein turnover.

“…It has previously been shown that the increased rates of protein break-down after denervation (Goldberg, 1969;Goldspink, 1976) can be inhibited by direct electrical stimulation of isolated muscles . Although Goldberg et al (1975) found no change in protein synthesis of skeletal muscle after electrical stimulation in vitro, Peterson & Lesch (1972) observed an increased incorporation of amino acids into proteins of the papillary muscle of the heart after repeated stimulations. Also in keeping with the present study Hamosh, Lesch, Baron & Kaufman (1967) found increased rates of protein synthesis during work-induced hypertrophy of skeletal muscle.…”

Rapid Increase in Cardiac Adrenomedullin Gene Expression Caused by Acute Pressure Overload. Effect of the Renin-Angiotensin System on Gene Expression.

“…22 The amount of cardiac hypertrophy is the summation of changes in corresponding rates of myocardial protein synthesis and degradation. The synthesis of myocardial protein is not only affected by mechanical stress, 23,24 but also by Ang II. 24 On the basis of these findings, cardiac AM gene transcription is also enhanced by the stimulation of cardiac protein synthesis, such as that through mechanical stress and/or RAS, as a result of different loading conditions.…”

Role of tissue angiotensin II in myocardial remodelling induced by mechanical stress

“…Peterson was the first to report that stretch of quiescent papillary muscle accelerates protein synthesis. 3 It was subsequently shown that elevation of aortic pressure increases protein synthesis in beating-perfused hearts. 4 In addition, Cooper et al 5 reported that in aorta-constricted cats, papillary muscle whose tendon has been cut to release tension does not represent hypertrophy, whereas neighbouring uncut papillary muscle shows marked hypertrophy, and that cardiac hypertrophy is induced by pressure overload even under the denervation of ventricular adrenoceptors.…”