ANGIOTENSIN-II (AII) AND ADRENAL-GLAND AII RECEPTORS IN RATS WITH CONGENITAL HYPOTHYROIDISM

Plasma angiotensin II (AII) concentration, plasma renin concentration (PRC), lung angiotensin-converting enzyme (ACE) activity and adrenal gland AII receptor isoforms have been evaluated in the postnatal development of the rat, in order to determine the alterations of the renin-angiotensin system (RAS) which occur in congenital hypothyroidism. The developmental AII profiles observed in control and hypothyroid rats were quite similar. Thus, All was elevated at birth and declined at week 5 of life to reach adult values. However, AII levels were lower in hypothyroid than in euthyroid animals before their stabilization. On the other hand, PRC in newborn hypothyroid and euthyroid animals was higher than in adulthood, being significantly increased immediately after birth in hypothyroid rats. Pulmonary ACE activity in both experimental groups was low at birth and increased with age. This increase was greater in euthyroid rats than in congenitally hypothyroid animals from day 28 of life. These results confirm that plasma AII levels in rats are predominantly controlled by plasma renin activity, although other factors, such as renin substrate availability, may be responsible for the reduced plasma AII concentration in congenital hypothyroidism during the first weeks of life. The developmental profile of the adrenal gland AII receptor showed four isoforms, with pl values of 6.8, 6.7, 6.5 and 6.3. AII receptor-complex expression increased with age but, in congenitally hypothyroid rats, a higher induction of AII receptor isoforms migrating to pl 6-8, 6.5 and 6.3 was observed. These findings show that thyroid hormone deficiency in early life can have an important role in the postnatal induction of the RAS components, which may be essential for the regulation of blood pressure, and for fluid and electrolyte balance in developing rats.