Oestrogen inhibits salt-dependent hypertension by suppressing GABAergic excitation in magnocellular AVP neurons.

AIMS: Abundant evidence indicates that oestrogen (E2) plays a protective role against hypertension. Yet, the mechanism underlying the antihypertensive effect of E2 is poorly understood. In this study, we sought to determine the mechanism through which E2 inhibits salt-dependent hypertension. METHODS AND RESULTS: To this end, we performed a series of in vivo and in vitro experiments employing a rat model of hypertension that is produced by deoxycorticosterone acetate (DOCA)-salt treatment after uninephrectomy. We found that E2 prevented DOCA-salt treatment from inducing hypertension, raising plasma arginine-vasopressin (AVP) level, enhancing the depressor effect of the V1a receptor antagonist (Phenylac1,D-Tyr(Et)2,Lys6,Arg8,des-Gly9)-vasopressin, and converting GABAergic inhibition to excitation in hypothalamic magnocellular AVP neurons. Moreover, we obtained results indicating that the E2 modulation of the activity and/or expression of NKCC1 (Cl- importer) and KCC2 (Cl- extruder) underpins the effect of E2 on the transition of GABAergic transmission in AVP neurons. Lastly, we discovered that, in DOCA-salt-treated hypertensive ovariectomized rats, CLP290 (prodrug of the KCC2 activator CLP257, intraperitoneal injections) lowered blood pressure, and plasma AVP level and hyperpolarized GABA equilibrium potential to prevent GABAergic excitation from emerging in the AVP neurons of these animals. CONCLUSION: Based on these results, we conclude that E2 inhibits salt-dependent hypertension by suppressing GABAergic excitation to decrease the hormonal output of AVP neurons.

Excessive maternal salt intake gives rise to vasopressin-dependent salt sensitivity of blood pressure in male offspring.

Salt sensitivity of blood pressure (SSBP) is a trait carrying strong prognostic implications for various cardiovascular diseases. To test the hypothesis that excessive maternal salt intake causes SSBP in offspring through a mechanism dependent upon arginine-vasopressin (AVP), we performed a series of experiments using offspring of the rat dams salt-loaded during pregnancy and lactation with 1.5% saline drink ("experimental offspring") and those with normal perinatal salt exposure ("control offspring"). Salt challenge, given at 7-8 weeks of age with either 2% saline drink (3 days) or 8% NaCl-containing chow (4 weeks), had little or no effect on systolic blood pressure (SBP) in female offspring, whereas the salt challenge significantly raised SBP in male offspring, with the magnitude of increase being greater in experimental, than control, rats. Furthermore, the salt challenge not only raised plasma AVP level more and caused greater depressor responses to V1a and V2 AVP receptor antagonists to occur in experimental, than control, males, but it also made GABA excitatory in a significant proportion of magnocellular AVP neurons of experimental males by depolarizing GABA equilibrium potential. The effect of the maternal salt loading on the salt challenge-elicited SBP response in male offspring was precluded by maternal conivaptan treatment (non-selective AVP receptor antagonist) during the salt-loading period, whereas it was mimicked by neonatal AVP treatment. These results suggest that the excessive maternal salt intake brings about SSBP in male offspring, both the programming and the expression of which depend on increased AVP secretion that may partly result from excitatory GABAergic action.

Observational threat conditioning is induced by circa-strike activity burst but not freezing and requires visual attention.

Social transmission refers to a process in which an observer (OB) acquires new information about the environment including threat situations, through the action of familiar conspecifics. Recently, a number of studies employing observational threat conditioning (OTC) in which OB mice expressed defensive responses following indirect exposure to pair-housed partner mice (demonstrator: DE) which were receiving repeated footshocks, have produced interesting insights into the social mechanisms of emotional transfer. However, the nature of the transmitted information or the critical cognitive processes involved in OTC is not clear. In a series of experiments, we investigated the key elements involves in triggering socially-induced defensive responses. In Exp.1, we compared the effectiveness in conveying a threat of two different types of defensive reactions of DEs: the circa-strike activity burst (CSAB) vs. freezing. The results show that the CSAB is more effective than freezing in inducing defensive freezing in an OB. In Exp. 2, we investigated different types of the OBs' defensive responses by measuring their change in head orientation or their "gazing" at the DEs, and their temporal synchrony with the DEs' defensive reactions in the form of their CSAB. The results show that OBs' gazing was significantly correlated with the DEs' CSAB, especially the DEs' jumping behavior, but not with the freezing of the DEs, indicating that jumping is a more effective trigger stimulus in inducing attentional capture in conspecific partner animals. In Exp. 3, the role of visual information was tested. The result shows that the OBs' level of freezing was significantly reduced when visual information was blocked by an opaque partition. In Exp. 4, to confirm the critical role of visual attention, we introduced distracting flashing lights, which were switched on and off at random intervals during the conditioning process. With all other conditions being maintained unaltered, the OBs in the distractor condition displayed a significantly decreased level of freezing, indicating that the visual attention paid to the DEs by the OBs during the conditioning process was critical for the social transmission of threat. Taken together, the results of the current study strongly suggest that socially transmitted defensive behavior is dependent on the specific behavioral elements of a DE's defensive behavior, and moreover, that a visual attentional process is required during the OTC.

Fabrication of flexible carbon nanotube field emitter arrays by direct microwave irradiation on organic polymer substrate.

Carbon nanotubes (CNTs) were directly synthesized on flexible polymer substrates without damage of polymer by microwave irradiation. Cobalt was used as the catalysts, and the synthesis was done in the atmospheric pressure with an acetylene carbon source. Only 5 s was required for the synthesis of well-graphitized CNTs. Field emission measurements revealed that this flexible CNT field emitter array has a great potential for the flexible field emission displays (FEDs).