The proposed studies will investigate regulation of growth, differentiation, and intrinsic beating rate of fetal rat heart by autonomic nerves, circulating factors and mechanisms intrinsic to the heart. Neural, hormonal and cardiac controls of cardiac development will be isolated by studying hearts maturing in an in vivo culture system, the anterior chamber of the eye of a host rat (i.e., in oculo). The following hypotheses will be tested: 1. Sympathetic innervation of heart tissue maturing in oculo causes myocyte hypertrophy and promotes differentiation into adult-like heart tissue. 2. Circulating catecholamines contribute to the growth, differentiation and determination of intrinsic beating rat of heart tissue maturing in oculo. 3. Growth, differentiation, and intrinsic beating rate of heart tissue developing in oculo are regulated by both sympathetic and parasympathetic innervation. 4. Autonomic innervation ceases to influence cardiac growth, differentiation, and intrinsic beating rate by 2 months in oculo. 5. Thyroid hormone promotes growth, differentiation and intrinsic beating rate of fetal heart cultured in oculo both by direct action and by increasing sensitivity to sympathetic stimulation. Cardiac growth will be measured by increases in size of transplanted atria and ventricles. The sizes of myocytes from implanted heart tissue will be measured to identify growth by hypertrophy. Differentiation from fetal to adult-like heart tissue will be examined by ultrastructural and biochemical criteria (i.e. electron microscopy and myosin isoenzyme composition). Intrinsic heart rate will be measured from in oculo atria after combined beta-adrenergic and muscarinic receptor blockade. With the in oculo culture system, heart development can be studied under conditions where neural and hormonal influences can be selectively controlled without changing hemodynamic load. This model provides a method for studying interactions among developing cardiovascular target organs, their autonomic innervation and their hormonal milieu. Early developmental influences may modulate genetically programmed maturation and contribute to subsequent individual differences in cardiovascular regulation and in the predisposition to cardiovascular diseases such as hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HL039048-05
Application #
3471533
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1987-07-01
Project End
1994-06-30
Budget Start
1991-07-01
Budget End
1994-06-30
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
Schools of Arts and Sciences
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Torres, A; Tucker, D C (1995) Glucocorticoid stimulation interacts with sympathetic innervation to affect cardiac development in oculo. Pediatr Res 38:479-84
Love, T C; Tucker, D C (1995) Timing of sympathetic innervation affects growth of myocardium in oculo. Am J Physiol 269:H140-8
Tucker, D C; Umeda, P K (1995) Rapid conversion from beta-MHC to alpha-MHC mRNA expression in embryonic rat ventricle cultured in oculo is not dependent on thyroid hormone or testosterone. J Mol Cell Cardiol 27:1415-25
Haskell, J F; Tucker, D C (1994) Binding of insulin-like growth factors (IGF-I and IGF-II) to the IGF-II/mannose 6-phosphate receptor in fetal rat myocardium. Endocrinology 135:231-9
Torres, A; Tucker, D C (1993) Effects of thyroid hormones on cardiac development in oculo. Am J Physiol 264:H244-51
Hunt, R A; Tucker, D C (1993) Developmental sensitivity to high dietary sodium chloride in borderline hypertensive rats. Hypertension 22:542-50
Tucker, D C; Askari, M; Bishop, S P (1992) Effects of sympathetic innervation on size of myocytes in embryonic rat heart cultured in oculo. J Mol Cell Cardiol 24:925-35
Tucker, D C; Torres, A (1992) Adrenal hormones interact with sympathetic innervation to modulate growth of embryonic heart in oculo. Am J Physiol 262:H318-25
Abrahamson, D R; St John, P L; Pillion, D J et al. (1991) Glomerular development in intraocular and intrarenal grafts of fetal kidneys. Lab Invest 64:629-39
Fisher, L D; Tucker, D C (1991) Air jet noise exposure rapidly increases blood pressure in young borderline hypertensive rats. J Hypertens 9:275-82

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