The usual model of intermittent hypoxia (sleep apnoea) corresponds to repeated episodes of hypoxia from a few seconds to a few hours interspersed with episodes of normoxia. The aim of this study was to evaluate in rats the effect of two periods of intermittent exposure for 2 months to hypoxia (IHX1,24 h in hypoxia (428 Torr), 24 h in normoxia; IHX2,48 h in hypoxia (428 Torr), 24 h in normoxia) as a new model of hypoxia simulating intermittent exposure to high altitude experienced by Andean miners. We assessed the haematological parameters, time course of resting heart rate and systolic blood pressure. We also evaluated the expression of adrenergic and muscarinic receptors. IHXl and IHX2 produced an increase in haematocrit, haemoglobin concentration and mean corpuscular volume as previously seen in most hypoxic models. IHXl and IHX2 induced a simiiar sustained elevation of systolic blood pressure (132 k 2 and 135 f 3 mmHg, respectively, vs. the control level of 121 & 16 mmHg) after I0 days of exposure without change in heart rate. Right ventricular (RV) hypertrophy (225 f 13 and 268 k 15 mg g-I, vs. 178 k 7 mg g-') and downregulation of a,-adrenoceptor (RV 127 k 21 and 94 k 16 fmol mg-' vs. 157 f 8 fmol mg-'; left ventricle (LV): 141 f 5 and 126 f 9 fmol mg-' vs. 152 f 5 fmol mg-') have been found in both groups, with right ventricular hypertrophy being greater and a,-adrenoceptor density being lower in IHX2 than in HX1 groups. These data indicate that both parameters are related to the time of exposure to hypoxia. IHXl and IHXZ produced the same magnitude of upregulation of muscarinic receptors (LV, 60%; RV, 40%), and no change in /3-adrenoceptors. In conclusion, exposure to intermittent hypoxia led to polycythaemia and RV hypertrophy as observed in other types of hypoxia. A specific cardiovascular response was seen, that is an increase in blood pressure without change in heart rate, which was different from the one observed in episodic and chronic hypoxia. Furthermore, this model involved specific modifications of a,-adrenergic and muscarinic expression. Expen 'mental Physiologv (2002) 87.4,453-460.

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Reduction of the protein content from 25 to 8% casein in the diet of pregnant rats results in impaired neocortical long-term potentiation (LTP) of the offspring together with lower visuospatial memory performance. The present study was aimed to investigate whether this type of maternal malnutrition could result in modification of plastic capabilities of the entorhinal cortex (EC) in the adult progeny. Unlike normal eutrophic controls, 55–60-day-old prenatally malnourished rats were unable to develop LTP in the medial EC to tetanizing stimulation delivered to either the ipsilateral occipital cortex or the CA1 hippocampal region. Tetanizing stimulation of CA1 also failed to increase the concentration of brain-derived neurotrophic factor (BDNF) in the EC of malnourished rats. Impaired capacity of the EC of prenatally malnourished rats to develop LTP and to increase BDNF levels during adulthood may be an important factor contributing to deficits in learning performance having adult prenatally malnourished animals.

Chronic cold stress applied to adult rats activates ovarian sympathetic innervation and develops polycystic ovary (PCO) phenotype. The PCO syndrome in humans originates during early development and is expressed before or during puberty, which suggests that the condition derived from in utero exposure to neural-or metabolic-derived insults. We studied the effects of maternal sympathetic stress on the ovarian follicular development and on the onset of puberty of female offspring. Timed pregnant rats were exposed to chronic cold stress (4 8C, 3 h/daily from 1000 to 1300 h) during the entire pregnancy. Neonatal rats exposed to sympathetic stress during gestation had a lower number of primary, primordial, and secondary follicles in the ovary and a lower recruitment of primary and secondary follicles derived from the primordial follicular pool. The expression of the FSH receptor and response of the neonatal ovary to FSH were reduced. A decrease in nerve growth factor (NGF) mRNA was found without change in the low-affinity NGF receptor. The FSH-induced development of secondary follicles was decreased. At puberty, estradiol plasma levels decreased without changes in LH plasma levels. Puberty onset (as shown by the vaginal opening) was delayed. Ovarian norepinephrine (NE) was reduced; there was no change in its metabolite, 3-methoxy-4-hydroxyphenylglycol, in stressed rats and no change in NE turnover. The changes in ovarian NE in prepubertal rats stressed during gestation could represent a lower development of sympathetic nerves as a compensatory response to the chronically increased NE levels during gestation and hence participate in delaying reproductive performance in the rat.

Prenatally malnourished rats develop hypertension in adulthood, in part through increased α1-adrenoceptor-mediated outflow from the paraventricular nucleus (PVN) to the sympathetic system. We studied whether both α1-adrenoceptor-mediated noradrenergic excitatory pathways from the locus coeruleus (LC) to the PVN and their reciprocal excitatory CRFergic connections contribute to prenatal undernutrition-induced hypertension. For that purpose, we microinjected either α1-adrenoceptor or CRH receptor agonists and/or antagonists in the PVN or the LC, respectively. We also determined the α1-adrenoceptor density in whole hypothalamus and the expression levels of α1A-adrenoceptor mRNA in the PVN. The results showed that: (i) agonists microinjection increased systolic blood pressure and heart rate in normotensive eutrophic rats, but not in prenatally malnourished subjects; (ii) antagonists microinjection reduced hypertension and tachycardia in undernourished rats, but not in eutrophic controls; (iii) in undernourished animals, antagonist administration to one nuclei allowed the agonists recover full efficacy in the complementary nucleus, inducing hypertension and tachycardia; (iv) early undernutrition did not modify the number of α1-adrenoceptor binding sites in hypothalamus, but reduced the number of cells expressing α1A-adrenoceptor mRNA in the PVN. These results support the hypothesis that systolic pressure and heart rate are increased by tonic reciprocal paraventricular–coerulear excitatory interactions in prenatally undernourished young-adult rats.

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We previously reported that centrally-induced sympathetic activation in response to cold stress is associated with a polycystic ovarian condition in rats, and thyrotrophin-releasing hormone (TRH) released locally from the magnocellular region of the paraventricular nucleus (PVN) appears to be involved in this activation. Because TRH neurones express NMDA glutamate receptors, in the present study, we investigated the role of glutamate in the increased release of TRH from magnocellular neurones induced by cold stress and its relationship to ovarian neurotransmission. Animals with a push-pull cannula stereotaxically implanted into the magnocellular portion of the PVN were exposed to cold stress (4 degrees C for 64 h) and subjected to intracerebral perfusion. Perfusate fractions were obtained and analysed by high-performance liquid chromatography to measure glutamate and GABA levels. Glutamate, but not GABA, release increased significantly in animals perfused under cold exposure. In vivo administration of glutamate to the PVN increased TRH release. Injection of MK-801 into the magnocellular portion of the PVN reduced ovarian noradrenaline turnover and led to an increase in catecholamine concentration from the adrenal glands and celiac ganglia. Taken together, the results obtained in the present study strongly suggest that glutamate release from the magnocellular PVN is sensitive to cold stress and that glutamate acts through the NMDA receptor to mediate cold-induced TRH release. This in turn triggers hypothalamic-ovarian pathway activation, which might be responsible for the polycystic condition induced by cold stress and other ovarian pathologies characterised by increased sympathetic discharge.

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