Integrative studies on central osmolality receptive mechanisms : Modification by novel peptides and environmental stress

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To elucidate the mechanisms responsible for adaptive responses following intracerebroventricular(i.c.v.) administration of hypertonic saline(HS), in vivo and in vitro studies have been performed using immunohistochemical, neurochemical, and electrophysiological methods. The results obtained are as follows :(1)The quantitative relationship between the intracerebroventricularly(i.c.v.) administered HS concentration and the expression of Fos-like immunoreactivity(FLI) in brain regions involved in the homeostasis of body fluid has been examined. The regions examined were the organum vasculosum lamina terminalis(OVLT), the median preoptic nucleus(MnPO), the subfornical organ(SFO), the paraventricular nucleus(PVN), the supraoptic nucleus(SON) of the hypothalamus, the nucleus of the solitary tract(NTS), and the area postrema(AP). HS was delivered in conscious rats with attention to the actual changes in central [Na^+]. The changes in cerebrospinal fluid [Na^+] during i.c.v. administration of … More HS were compatible with those expected for thermal dehydration. FLI increased in a dose-dependent manner in the PVN and NTS. Although the pressor responses during central salt loading were not significantly affected by pretreatment with vasopressin V_1 receptor antagonist OPC-21268, FLI expression in the PVN was significantly augmented. The result suggests that the peripheral vasopressin system participates in negative feedback to modulate neuronal activities in the PVN, probably through direct action at the PVN in response to central osmotic and /or Na stimulation.(2)Direct perfusion of the PVN region with HS was performed in conscious rats by using an in vivo brain microdialysis technique. The extracellular concentration of nitric oxide(NO) metabolites was measured, as were the blood pressure(BP) and heart rate(HR). HS perfusion increased the BP, HR, and NO metabolite levels in the PVN. Pretreatment with N^g-methyl-L-arginine (L-NMMA), an inhibitor of NO synthase, attenuated the increases in the BP and HR induced by direct infusion of HS. The result suggests that local perfusion of the PVN region with HS elicits a local release of NO, which may mediate the production of cardiovascular responses.(3)Extracellular recordings of neurons in the PVN of consciously, freely moving male rats were performed using a movable electrode system. Single-unit activities were examined for their spontaneous firing patterns, as well as responses to intero-and extero-ceptive stressors, including disturbance in BP, water deprivation, air-jet stimulation, and systemic administration of cholecystoknin-8(CCK). On the basis of the responses to these stressors, putative vasopressin-secreting neurons could be identified. This technique may contribute to understanding of local neural mechanisms within the PVN that are responsible for stress responses in conscious rats. Less