In humans, there is a significant decrease in serum T(3) and increase in rT(3) at different time points after myocardial infarction, whereas serum TSH and T(4) remain unaltered. We report here a time course study of pituitary-thyroid function and thyroid hormone metabolism in rats subjected to myocardial infarction by left coronary ligation (INF). INF- and sham-operated animals were followed by serial deiodination assays and thyroid function tests, just before, and 1, 4, 8, and 12 wk after surgery. At 4 and 12 wk after INF, liver type 1 deiodinase activity was significantly lower, confirming tissue hypothyroidism. Type 3 deiodinase (D3) activity was robustly induced 1 wk after INF only in the infarcted myocardium. Reminiscent of the consumptive hypothyroidism observed in patients with large D3-expressing tumors, this induction of cardiac D3 activity was associated with a decrease in both serum T(4) ( approximately 50% decrease) and T(3) (37% decrease), despite compensatory stimulation of the thyroid. Thyroid stimulation was documented by both hyperthyrotropinemia and radioiodine uptake. Serum TSH increased by 4.3-fold in the first and 3.1-fold in the fourth weeks (P < 0.01), returning to the basal levels thereafter. Thyroid sodium/iodide-symporter function increased 1 wk after INF, accompanying the increased serum TSH. We conclude that the acute decrease in serum T(4) and T(3) after INF is due to increased thyroid hormone catabolism from ectopic D3 expression in the heart.

The present work was carried out to investigate the role of angiotensin II type 1 (AT 1 ) receptors in nocturnal thirst and sodium appetite induced by classical models of osmotic and sodium depletion challenges in ovariectomized rats chronically treated with oil or oestradiol benzoate (EB, 20 μg per animal, S.C. daily). In both conditions, the animals were given saline or losartan (108 nmol per animal, I.C.V.), a selective AT 1 receptor blocker. Oestrogen therapy significantly reduced the water intake induced by water deprivation, sodium depletion produced by frusemide injected 24 h before, and S.C. acute frusemide plus captopril injection (FUROCAP protocol), with no alteration following S.C. hypertonic saline injection. In contrast, EB therapy decreased the salt intake induced by sodium depletion and FUROCAP protocols, with no alteration following water deprivation and S.C. hypertonic saline injection. Central AT 1 blockade inhibited the dipsogenic response induced by water deprivation, osmotic stimulation, chronic sodium depletion and FUROCAP protocols and inhibited the natriorexigenic response induced by sodium depletion in ovariectomized rats. Oestrogen therapy significantly attenuated the losartan-induced antidipsogenic and antinatriorexigenic actions following sodium depletion and FUROCAP protocols. These results indicate that ovariectomized rats express increased AT 1 receptor signalling related to thirst and sodium appetite responses. Oestrogen therapy and brain AT 1 receptor blockade weakened or markedly decreased the behavioural responses during the nocturnal period, a time at which brain angiotensinergic activity is expected to be more prominent. Finally, we demonstrated through different experimental protocols a clear-cut influence of oestrogenic status on the behavioural AT 1 -induced signalling response.

-Estrogen receptors are located in important brain areas that integrate cardiovascular and hydroelectrolytic responses, including the subfornical organ (SFO) and supraoptic (SON) and paraventricular (PVN) nuclei. The aim of this study was to evaluate the influence of estradiol on cardiovascular and neuroendocrine changes induced by hemorrhagic shock in ovariectomized rats. Female Wistar rats (220 -280 g) were ovariectomized and treated for 7 days with vehicle or estradiol cypionate (EC, 10 or 40 g/kg, sc). On the 8th day, animals were subjected to hemorrhage (1.5 ml/100 g for 1 min). Hemorrhage induced acute hypotension and bradycardia in the ovariectomized-oil group, but EC treatment inhibited these responses. We observed increases in plasma angiotensin II concentrations and decreases in plasma atrial natriuretic peptide levels after hemorrhage; EC treatment produced no effects on these responses. There were also increases in plasma vasopressin (AVP), oxytocin (OT), and prolactin levels after the induction of hemorrhage in all groups, and these responses were potentiated by EC administration. SFO neurons and parvocellular and magnocellular AVP and OT neurons in the PVN and SON were activated by hemorrhagic shock. EC treatment enhanced the activation of SFO neurons and AVP and OT magnocellular neurons in the PVN and SON and AVP neurons in the medial parvocellular region of the PVN. These results suggest that estradiol modulates the cardiovascular responses induced by hemorrhage, and this effect is likely mediated by an enhancement of AVP and OT neuron activity in the SON and PVN.hemorrhage; female rats; supraoptic nuclei; paraventricular nuclei; arterial pressure; heart rate THE PRECISE REGULATION OF body fluids is essential for the metabolic function of virtually all cells in the body. A variety of mechanisms are activated to maintain plasma osmolality and blood volume within a very narrow range of values (3). For example, hypovolemia and/or hypotension induce vasopressin (AVP) and oxytocin (OT) release from the magnocellular neurons of the supraoptic (SON) and paraventricular (PVN) nuclei in the hypothalamus (3, 56). It is estimated that a decrease of 10 -20% in total blood volume induces the release of AVP in several species. This neurosecretory response is modulated by peripheral baroreceptors in the aortic arch and carotid sinus, cardiopulmonary volume receptors, and angiotensin II (ANG II) (50, 65).The precise role of estrogen in maintaining body fluid homeostasis is not yet fully understood (16). Our group has previously reported that ANG II type 1 (AT 1 ) receptors are involved in the regulation of water and hypertonic saline intake in ovariectomized (OVX) rats during the nocturnal period (37, 38). In addition, several reports have suggested that estrogen has modulatory effects on cardiovascular function, as evidenced by the cardiovascular changes observed in postmenopausal women, OVX rats, and, possibly, females of other species during senescence (12, 46). These effects occur by estrogen's action on the...

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Angiotensin II (Ang II) acts on Ang II type 1 (AT1) receptors located in the organum vasculosum and subfornical organ (SFO) of the lamina terminalis as a main facilitatory mechanism of sodium appetite. The brain serotonin (5‐HT) system with soma located in the dorsal raphe nucleus (DRN) provides a main inhibitory mechanism. In the present study, we first investigated the existence of Ang II AT1 receptors in serotonergic DRN neurones. Then, we examined whether whole body sodium depletion affects the gene expression of the AT1a receptor subtype and the presumed functional significance of AT1 receptors. Using confocal microscopy, we found that tryptophan hydroxylase‐2 and serotonin neurones express AT1 receptors in the DRN. Immunofluorescence quantification showed a significant reduction in 5‐HT content but no change in AT1 receptor expression or AT1/5‐HT colocalisation in the DRN after sodium depletion. Whole body sodium depletion also significantly increased Agtr1a mRNA expression in the SFO and DRN. Oral treatment with the AT1 receptor antagonist losartan reversed the changes in Agtr1a expression in the SFO but not the DRN. Losartan injection into either the DRN or the mesencephalic aqueduct had no influence on sodium depletion‐induced 0.3 mol L‐1 NaCl intake. The results indicate the expression of Agtr1a mRNA in the DRN and SFO as a marker of sodium depletion. They also suggest that serotonergic DRN neurones are targets for Ang II. However, the function of their AT1 receptors remains elusive.