Early and late effect of neonatal hypo- and hyperthyroidism on coronary capillary geometry and long-term heart function in rat.

Abstract

The aim of the present study was two-fold: (1) to examine the effect of hyper- and hypothyroidism on the developing coronary capillary network in neonatal rats, and (2) to determine in adult rats that had re-established euthyroid status whether long-term changes in capillary geometry or cardiac function had been induced by either neonatal thyroid condition. Two-day-old rats were treated every other day for 12 or 28 days with either 3,3'5-triiodo-l-thyronine or 0.05% 6-n-propylthiouracil. After this time, treatment was stopped and in two-thirds of the rats morphometric examination of capillary geometry and 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 were assessed. 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 hyperthyroid rats (P < 0.05), but attenuated capillary growth in hypothyroid rats. The elicited capillary growth response appeared to be more dependent on altered tissue maturation than on cardiac growth rate. After discontinuing treatment both neonatal thyroid conditions induced a deficit in left ventricular growth (P < 0.01). Furthermore, neonatal hyperthyroidism appeared to inhibit subsequent capillary growth in distal regions of the capillary bed in addition to inducing lasting positive chronotropic and inotropic effects on cardiac function (P < 0.05). Neonatal hypothyroidism did not produce any lasting changes in capillarization or in cardiac function. 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.