The proposed studies will examine the influence of sympathetic and parasympathetic innervation and circulating catecholamine stimulation on the growth, differentiation and intrinsic beating rate of the fetal rat heart. Neural and cardiac controls of cardiac development will be isolated by studying hearts maturing in an in vivo organ culture system, the anterior chamber of the eye of host rat. The following hypotheses will be tested: 1. By morphological and electrophysiological criteria, myocardial tissue cultured in oculo develops to an adult-like stage from the fetal stage at which it is implanted. 2. Circulating catecholamines contribute to the growth, differentiation, and determination of intrinsic beating rate of heart tissue maturing in oculo. 3. Both the sympathetic and parasympathetic nervous systems regulate growth, differentiation, and intrinsic beating rate of heart tissue developing in oculo. 4. Autonomic innervation ceases to influence cardiac growth, differentiation, and intrinsic beating rate after 30 days in oculo. Cardiac growth will be measured by increases in size of the transplanted hearts. The sizes of myocytes from implanted heart tissue will be measured to distinguish between growth by hypertrophy vs hyperplasia. Differentiation from fetal to adult-like heart tissue will be confirmed by ultrastructural criteria (electron microscopy). Intrinsic heart rate will be measured in cultured tissue after combined beta-adrenergic and muscarinic receptor blockade. With the in oculo culture system, development of the heart can be studied under conditions where neural influences can be selectively controlled. This model provides a method for studying interactions between developing cardiovascular target organs and their autonomic innervation. These early developmental influences may modulate genetically programmed maturation, contributing to subsequent individual differences in cardiovascular regulation and in the predisposition to cardiovascular diseases such as hypertension.
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| Tucker, D C (1990) Genetic, neurohumoral, and hemodynamic influences on spontaneously hypertensive rat heart development in oculo. Hypertension 15:247-56 |
