Immunocytochemical studies have shown that adrenalectomy produces changes in the content and distribution of [arginine-8]vasopressin (AVP) immunoreactivity in the paraventricular nucleus of the hypothalamus. The purpose of this study was to determine whether manipulation of adrenal hormones affects the levels of AVP mRNA. In situ hybridization assays with highly specific synthetic oligodeoxyribonucleotide probes and immunocytochemistry were used to detect the distribution of AVP mRNA and AVP-immunoreactive perikarya. AVP mRNA is codistributed with AVP immunoreactivity in the posterior magnocellular subdivision of the paraventricular nucleus and its accessory nuclei, the supraoptic nucleus and the suprachiasmatic nucleus. In adrenalectomized rats, the density and distribution of the hybridization signal were increased in the paraventricular nucleus; a 2-fold increase in the area comprising the signal was observed. At the cellular level, silver grains were detected in corticotropin-releasing-factor-immunoreactive neurons throughout the medial parvocellular subdivision of the paraventricular nucleus. No changes were seen in the distribution of AVP mRNA in the supraoptic or suprachiasmatic nuclei. Treatment with dexamethasone prevented the increase in AVP mRNA produced by adrenalectomy. In contrast, adrenalectomy did not alter the hybridization signal obtained with a probe for a-tubulin mRNA. These results suggest, at the cellular level, that adrenalectomy induces a glucocorticoid-sensitive stimulation of AVP mRNA synthesis in the central nervous system. Thus, considerable plasticity in gene expression is retained in the hypothalamus of the adult rat.The discrete anatomical organization of hypothalamic neurosecretory neurons within the paraventricular nucleus (PVN) has established this region as a unique site to study the neurohypophyseal secretory system. [arginine-8]Vasopressin (AVP) and oxytocin are contained within neurons of the PVN and the supraoptic nucleus (SON) (1, 2) and are involved in both autonomic and neurosecretory functions (3, 4). The axons emanating from these perikarya form the hypothalamoneurohypophyseal tracts, which project to the pars nervosa where AVP is released from their terminal endings (5,6). However, AVP has been detected in axon terminals within the external zone of the median eminence (7), suggesting that it may be involved, to some extent, in regulating anterior pituitary functions. Unlike the neurohypophyseal projection, the majority of AVP-immunoreactive axon terminals in the median eminence originate from neurons within the medial parvocellular subdivision of the PVN (8). Biochemical studies have confirmed quantitatively that adrenalectomy increases AVP immunoreactivity (7, 9). After adrenalectomy, corticotropin-releasing factor (CRF) and AVP were reported to be colocalized within neurons in the medial parvocellular region of the PVN (10, 12). This finding is of particular interest because immunocytochemical studies have shown that adrenalectomy produces a dexamethasonesen...

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The changes in transcutaneous oxygen saturation (SaO2%) and airway responses to inhaled histamine and leukotriene C4 (LTC4) were examined in 10 asthmatic patients, and the effect of inhaled LTC4 (16 nmol) on cardiopulmonary hemodynamics was examined in seven nonasthmatic patients undergoing diagnostic cardiac catheterization. In asthmatic patients, LTC4 produced oxygen desaturation on two occasions. At a lower dose (2.0 nmol) LTC4 produced a marked fall in SaO2% that lasted less than 15 min and occurred in the absence of significant bronchoconstriction as measured by changes in FEV1, FEF25-75, and SGaw. At a higher cumulative dose (7 nmol), LTC4 caused prolonged oxygen desaturation with slow recovery and this was associated with significant bronchoconstriction. In contrast, histamine inhalation produced a single response with a fall in both FEV1 and SaO2% of short duration. The dose-response characteristics of LTC4 and histamine on oxygen desaturation in asthmatic patients appear to differ significantly and probably are dependent on relative sensitivities of pulmonary vascular and bronchial smooth muscle to these agonists. A single inhaled dose of LTC4 in nonasthmatic subjects produced a marked drop in PaO2 with significant increase in AaPO2, and this was associated with a mean (SEM) decrease in FEV1 of 14% (2.5) from the baseline. The mean cardiac output fell by 15% (3.4) without significant changes in blood pressure and heart rate. There was no electrocardiographic evidence of myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)