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  • 1
    ISSN: 1573-4919
    Keywords: bradykinin ; HOE 140 ; enalapril maleate ; hypertrophy ; angiotensin 11 ; newborn heart
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Rapid growth of the left ventricle of the newborn pig heart can be restrained by treating piglets with the angiotensin converting enzyme inhibitor, enalapril maleate. This reduced rate of growth is reflected in vitro by reduced rates of ribosome formation and protein synthesis, and may be due to decreased availability of angiotensin II (All), a potentially hypertrophic agent; decreased numbers of All receptors; increased availability of bradykinin, a potentially antihypertrophic agent; or reduced hemodynamic load on the left ventricle. Because enalapril decreases degradation of bradykinin, the role of bradykinin as an inhibitor of cardiac growth in the newborn heart was investigated. Addition of 1 × 10−5 M bradykinin and 1 × 10−6 Menalapril to the perfusate of isolated hearts from 2 day old piglets did not significantly alter heart rate, contents of ATP or creatine phosphate or rates of ribosome formation or protein synthesis during 1 h of perfusion. Similarly, exposure of myocytes isolated from the left ventricular free wall of piglets to 5 × 10−6 M bradykinin for 72 h did not alter the rate of [3H]-phenylalanine incorporation into total protein. The reduced rate of left ventricular growth in vivo caused by enalapril administration was not reversed by simultaneous treatment with the specific bradykinin receptor antagonist, HOE 140. HOE 140 alone did not alter ventricular growth as compared to hearts from untreated piglets. In summary, these results demonstrate that the reduced rate of left ventricular growth in vivo and the reduced rate of ribosome formation and protein synthesis in the left ventricle in vitro after enalapril treatment of piglets is not the result of an inhibitory effect of bradykinin on cardiac growth.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Molecular and cellular biochemistry 176 (1997), S. 145-151 
    ISSN: 1573-4919
    Keywords: efficiency of protein synthesis ; capacity of protein synthesis ; peptide chain initiation ; ribosomal DNA transcription ; mechanical activity ; hormonal regulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Rapid cardiac growth depends upon faster synthesis than degradation of protein. The rate of protein synthesis is determined by the efficiency with which the existing components of the ribosome cycle make protein and by the quantity of the components that are present. The tissue content of RNA is taken as an index of the capacity of synthesis and efficiency is expressed as the amount of protein formed per amount of RNA over a certain time period. The efficiency of synthesis is regulated by hormones, including insulin, agents that increase cAMP, α-adrenergic agonists, endothelin I and angiotensin II. In addition, provision of non-carbohydrate substrates and mechanical factors such as stretch and contraction increase efficiency. Impaired energy availability as occurs in anoxic or ischemic muscle decreases efficiency. Increased phosphorylation of ribosomal protein, S6, or of the peptide chain initiation factor, elF-4E, have been suggested as mechanisms to regulate efficiency of mRNA translation. Increased efficiency of synthesis accounts for cardiac growth in the first few days following aortic banding, pulmonary artery constriction and thyroxine administration. Decreased efficiency accounts for cardiac atrophy in heterotopic transplanted hearts during the first 3 days following transplantation. The capacity of synthesis is increased by insulin, thyroid hormone, activators of protein kinase C, agents that increase cAMP, and endothelin-1. Stretch of the ventricular wall and contraction of cultured neonatal myocytes accelerates ribosome formation. An increased rate of ribosomal DNA transcription accounts for accelerated ribosome formation and depends on increased activity of a transcription factor, upstream binding factor (UBF). The activity of UBF is increased either by increased rates of synthesis or by phosphorylation of the protein. Increased capacity of synthesis is a major contributor to rapid cardiac growth in the newborn heart and after several days of pressure overload.
    Type of Medium: Electronic Resource
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