EARLY AND LATE EFFECT OF NEONATAL HYPOTHYROIDISM AND HYPERTHYROIDISM ON CORONARY CAPILLARY GEOMETRY AND LONG-TERM HEART FUNCTION IN RAT

Objective: The aim of the present study was two-fold: (1) to examine t he effect of hyper- and hypothyroidism on the developing coronary capi llary network in neonatal rats, and () to determine in adult rats that had re-established euthyroid status whether long-term changes in capi llary geometry or cardiac function had been induced bq either neonatal thyroid condition. Method: Two-day-old rats were treated every other day for 12 or 28 days with either 3,3',5-triiodo-1-thyronine or 0.05% 6-n-propylthiouracil. After this time? treatment was stopped and in tw o-thirds of the rats morphometric examination of capillary geometry an d immunohistochemical detection of proliferating cell nuclear antigen (PCNA) expression in endothelial cell nuclei were conducted. Remaining rats were weaned and grew to 80 days of age, at which time persistent changes in capillary geometry, PCNA expression and cardiac function w ere assessed. Results: Neonatal hyperthyroidism induced cardiomegaly ( P < 0.01), whereas neonatal hypothyroidism attenuated cardiac growth ( P < 0.01). Capillary numerical density, capillary segment lengths, and PCNA-labelling analysis indicated marked capillary growth in hyperthy roid rats (P < 0.05), but attenuated capillary growth in hypothyroid r ats. The elicited capillary growth response appeared to be mon depende nt on altered tissue maturation than on cardiac growth rate. After dis continuing treatment both neonatal thyroid conditions induced a defici t in left ventricular growth (P < 0.01). Furthermore, neonatal hyperth yroidism appeared to inhibit subsequent capillary growth in distal reg ions of the capillary bed in addition to inducing lasting positive chr onotropic and inotropic effects on cardiac function (P < 0.05). Neonat al hypothyroidism did not produce any lasting changes in capillarizati on or in cardiac function. Conclusions: Results suggest that neonatal thyroid status influences early growth and development of the coronary capillary network, possibly by regulating tissue maturation, as well as inducing lasting effects on subsequent cardiac and capillary growth and heart function.