Propranolol inhibits myocardial infarction-induced brown adipose tissue D2 activation and maintains a low thyroid hormone state in rats.

Considering the recognized role of thyroid hormones on the cardiovascular system during health and disease, we hypothesized that type 2 deiodinase (D2) activity, the main activation pathway of thyroxine (T4)-to-triiodothyronine (T3), could be an important site to modulate thyroid hormone status, which would then constitute a possible target for ß-adrenergic blocking agents in a myocardial infarction (MI) model induced by left coronary occlusion in rats. Despite a sustained and dramatic fall in serum T4 concentrations (60-70%), the serum T3 concentration fell only transiently in the first week post-infarction (53%) and returned to control levels at 8 and 12 weeks after surgery compared to the Sham group (P<0.05). Brown adipose tissue (BAT) D2 activity (fmol T4·min-1·mg ptn-1) was significantly increased by approximately 77% in the 8th week and approximately 100% in the 12th week in the MI group compared to that of the Sham group (P<0.05). Beta-blocker treatment (0.5 g/L propranolol given in the drinking water) maintained a low T3 state in MI animals, dampening both BAT D2 activity (44% reduction) and serum T3 (66% reduction in serum T3) compared to that of the non-treated MI group 12 weeks after surgery (P<0.05). Propranolol improved cardiac function (assessed by echocardiogram) in the MI group compared to the non-treated MI group by 40 and 57%, 1 and 12 weeks after treatment, respectively (P<0.05). Our data suggested that the beta-adrenergic pathway may contribute to BAT D2 hyperactivity and T3 normalization after MI in rats. Propranolol treatment maintained low T3 state and improved cardiac function additionally.

Propranolol inhibits myocardial infarction-induced brown adipose tissue D2 activation and maintains a low thyroid hormone state in rats

Considering the recognized role of thyroid hormones on the cardiovascular system during health and disease, we hypothesized that type 2 deiodinase (D2) activity, the main activation pathway of thyroxine (T4)-to-triiodothyronine (T3), could be an important site to modulate thyroid hormone status, which would then constitute a possible target for β-adrenergic blocking agents in a myocardial infarction (MI) model induced by left coronary occlusion in rats. Despite a sustained and dramatic fall in serum T4 concentrations (60-70%), the serum T3 concentration fell only transiently in the first week post-infarction (53%) and returned to control levels at 8 and 12 weeks after surgery compared to the Sham group (P<0.05). Brown adipose tissue (BAT) D2 activity (fmol T4·min-1·mg ptn-1) was significantly increased by approximately 77% in the 8th week and approximately 100% in the 12th week in the MI group compared to that of the Sham group (P<0.05). Beta-blocker treatment (0.5 g/L propranolol given in the drinking water) maintained a low T3 state in MI animals, dampening both BAT D2 activity (44% reduction) and serum T3 (66% reduction in serum T3) compared to that of the non-treated MI group 12 weeks after surgery (P<0.05). Propranolol improved cardiac function (assessed by echocardiogram) in the MI group compared to the non-treated MI group by 40 and 57%, 1 and 12 weeks after treatment, respectively (P<0.05). Our data suggested that the beta-adrenergic pathway may contribute to BAT D2 hyperactivity and T3 normalization after MI in rats. Propranolol treatment maintained low T3 state and improved cardiac function additionally.

Lipids analysis in hemolymph of African giant Achatina fulica (Bowdich, 1822) exposed to different photoperiods.

The influence of different photophases (0, 6, 12, 18 and 24 hours) on the triglycerides and total cholesterol contents in the hemolymph of A. fulica was evaluated, since there is no information in the literature about the influence of this factor on lipids metabolism in mollusks. After 2 and 4 weeks of exposure the snails were dissected. The cholesterol content at the 2nd and 4th weeks post exposure only varied significantly in the groups exposed at 24 hours and 0 hour of photophase, respectively. Probably, such increase may be a result of a rise in cholesterol biosynthesis and/or remodelling of cell membranes. There were no significant differences among the content of triglycerides in the snails exposed to 6, 12, 18 and 24 hours of photophase during two weeks. The snails exposed to intermediate photophase (6 and 12 hours) had the triglycerides content increased, ranging over values near to those observed in the group exposed to 0 hour. Results showed that triglycerides metabolism in A. fulica are more influenced by photoperiod than cholesterol metabolism. A negative relation is maintained between the triglycerides content in the hemolymph and the different photophases, with lower mobilisation of triglycerides under shorter photophases.

Maternal hypothyroxinemia impairs spatial learning and synaptic nature and function in the offspring.

Neurological deficits in the offspring caused by human maternal hypothyroxinemia are thought to be irreversible. To understand the mechanism responsible for these neurological alterations, we induced maternal hypothyroxinemia in pregnant rats. Behavior and synapse function were evaluated in the offspring of thyroid hormone-deficient rats. Our data indicate that, when compared with controls, hypothyroxinemic mothers bear litters that, in adulthood, show prolonged latencies during the learning process in the water maze test. Impaired learning capacity caused by hypothyroxinemia was consistent with cellular and molecular alterations, including: 1) lack of increase of phosphorylated c-fos on the second day of the water maze test; 2) impaired induction of long-term potentiation in response to theta-burst stimulation to the Schaffer collateral pathway in the area 1 of the hippocampus Ammon's horn stratum radiatum, despite normal responses for input/output experiments; 3) increase of postsynaptic density protein 95 (PSD-95), N-methyl-D-aspartic acid receptor subunit 1, and tyrosine receptor kinase B levels in brain extracts; and 4) significant increase of PSD-95 at the PSDs and failure of this molecule to colocalize with N-methyl-D-aspartic acid receptor subunit 1, as it was shown by control rats. Our findings suggest that maternal hypothyroxinemia is a harmful condition for the offspring that can affect key molecular components for synaptic function and spatial learning.

Effects of ageing and pharmacological hypothyroidism on pituitary-thyroid axis of Dutch-Miranda and Wistar rats.

To evaluate the ability of the aged rat pituitary to increase TSH secretion in response to major decreases in serum thyroid hormones, hypothyroidism was induced by methimazole in young and old, male and female, Dutch-Miranda and Wistar rats. Before MMI-treatment there were no differences in serum TSH of young and old rats, but serum T(4) was significantly decreased in aged rats from both genders and strains, while serum T(3) was significantly decreased in aged male rats from both strains, and in old Wistar females. MMI treatment significantly decreased serum T(4) and T(3) in all treated animals, and progressively increased serum TSH in both male and female rats, but the increase was significantly smaller in the elder rats. The pituitary TSH content was higher in Wistar than in Dutch-Miranda rats, of both genders, and was not significantly affected by age. MMI treatment decreased the pituitary TSH in both young and old Dutch-Miranda rats, but in the Wistar strain only the old females had a significant decrease. Our results show that the ability of the pituitary thyrotrophs to increase hormonal secretion in response to decreased levels of thyroid hormones is impaired in the old rat, even when the thyroid hormone levels are dramatically reduced.