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Schlagwörter:
lipopolysaccharide; osmotic stimulation; vasopressin; hypothalamic supraoptic and paraventricular nuclei
Zusammenfassung:
Vasopressin secreted by magnocellular neurones of the hypothalamic supraoptic and paraventricular nuclei is essential for water balance. In this study, we examined magnocellular neurone responses to osmotic stimulation in vehicle-injected controls or rats receiving an intraperitoneal (i.p.) injection of 250 microg/100 g of lipopolysaccharide (LPS), 3 h or 6 h earlier. LPS injection had no effect on plasma vasopressin concentrations in control rats but it caused marked and transient potentiation of the responses to a single i.p. injection of hypertonic saline (five- and two-fold, 3 and 6 h after LPS, respectively). The enhancement of plasma vasopressin responses was independent of plasma sodium concentrations or changes in blood pressure. Basal vasopressin mRNA expression in the paraventricular and supraoptic nuclei decreased slightly 6 h after LPS injection, without changes in vasopressin transcription as indicated by vasopressin heteronuclear (hn) RNA levels. Parvocellular neurones showed expected increases in vasopressin hnRNA expression following LPS injection and a further increase after i.p. hypertonic saline injection (due to the painful component). In contrast to magnocellular vasopressin mRNA expression, the effects of LPS and hypertonic saline injections in parvocellular neurones were additive and not synergistic. Light microscopic immunohistochemical examination revealed an increase in size of vasopressin but not oxytocin axonal terminals in the neural lobe 3 h after LPS injection. Osmotic stimulation caused marked depletion of vasopressin immunoreactivity in axonal terminals of the neural lobe in both control and LPS-pretreated rats. The changes in vasopressin axon terminals were accompanied by induction of interleukin (IL)-1 beta and IL-6 in the posterior pituitary. The data show that endotoxemia causes morphological and functional alterations of the hypothalamic neurohypophyseal system, resulting in facilitation rather than inhibition of vasopressin synthesis, and secretion in response to osmotic stimulation.
