Rapid Cardiac Growth Mechanical, Neural and Endocrine Dependence

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Rapid growth of the cardiac left ventricle is a hallmark of the neonatal period. During the first 2 weeks of life in the piglet, weight of the left ventricle increases 4 fold. The increase in weight is accompanied by approximately a 4 fold increase in myocyte volume indicating hypertrophic growth. Total RNA also increases approximately 4 fold indicating that the mechanism of growth involves greater ribosome content and greater capacity for protein synthesis. The rapid rate of ribosome formation and protein synthesis cannot be further accelerated in isolated perfused hearts by insulin, agents that increase 3',5'-cyclic monophosphate, α₁-adrenergic agonists or angiotensin II. In an attempt to slow cardiac growth and make it responsive to growthpromoting agonists, piglets are treated with an angiotensin converting enzyme inhibitor, enalapril maleate. Enalapril decreases left ventricular growth by 19% and total RNA content by 36%. When enalapril-treated hearts are perfused in vitro for 1 h, α₁-adrenergic agents restore rates of ribosome formation to control values but angiotensin II has no effect. In left ventricular myocytes that are cultured for 3 days, an α₁-adrenergic agonist and endothelin increases the rate of protein synthesis by 20 to 75% but angiotensin II has only a marginal effect (8%). These findings indicate that inhibition of growth by enalapril most likely is due to decreased ventricular pressure development that is secondary to peripheral vasodilation and a fall in mean arterial pressure. (Jpn Circ J 1997; 61: 645 - 649)