The release of inhibitory amino acids in the hypothalamus is tonically modified by impulses from aortic baroreceptors as a consequence of blood pressure fluctuations

Abstract

We investigated in conscious, freely moving rats whether the release of GABA, taurine and arginine in the hypothalamus is influenced by impulses originating from peripheral baroreceptors. The posterior hypothalamic nucleus was superfused with artificial cerebrospinal fluid through a push-push cannula and the release of amino acids was determined in the hypothalamic superfusate of control rats, as well as of rats after bilateral aortic denervation (AD). AD led to hypertension and increased the lability of arterial pressure. In sham-operated rats, intravenous infusion of phenylephrine increased blood pressure and the hypothalamic release of GABA and taurine. AD almost abolished the phenylephrine-induced release of the inhibitory amino acids. Similarly, the pressor response to hypervolaemia, elicited by blood injection, enhanced the release rates of GABA and taurine only in sham-operated rats. Baroreceptor unloading evoked either by intravenous infusion of nitroprusside, or by haemorrhage, decreased the release rates of GABA and taurine in sham-operated rats but not in AD rats. Electrical stimulation of the afferent aortic depressor nerve enhanced extracellular GABA and taurine in the posterior hypothalamic nucleus. The release rate of arginine was not influenced by alterations in baroreceptor activity either in sham-operated or in AD rats. The findings support the idea that, in the hypothalamus, GABA and taurine are involved in central blood pressure regulation. The release of these two amino acids seems to be driven tonically by baroreceptor impulses. Moreover, the findings indicate that the baroreceptors of the aortic arch play a crucial role in the mediation of changes in hypothalamic GABA and taurine outflow so as to counteract blood pressure fluctuations.

Chronic aortic denervation decreases anxiety and impairs social memory in rats

“…Several significant correlations such as the effects of the evoked lack of blood pressure stimuli to the CNS on the behaviour and on endocrine functions are not elucidated. In the present study bilateral aortic denervation caused, in agreement with previous data, hypertension, tachycardia and elevated blood pressure lability one and three months after the surgical intervention (Singewald et al 1997;Takeda et al 1989;Franchini and Krieger 1992;Krieger 1984). Hypertension was observed some days after bilateral aortic denervation (Singewald et al 1997;Osborn and England 1990;Kouvelas et al 2006) and arterial pressure lability hours after baroreceptor denervation (Alper et al 1987).…”

“…Afterwards, only the bAD group underwent a surgical exposition of carotid bifurcation and the vagus nerve, the superior cervical ganglion and the laryngeal nerve. Subsequently, laryngeal nerve and superior cervical ganglion were bilaterally separated from the vagi for 1 cm and severed (Singewald et al 1997;el-Mas et al 1994;Fink et al 1980). SHAM rats received similar cervical incisions and sternocledomastoids retractions, but the aortic depressor nerves, the laryngeal nerves and the superior cervical ganglia were neither isolated nor dissected leaving nerves, vessels and baroreceptors intact.…”

“…The incisions of both groups of rats, SHAM-and bAD group were closed using silk sutures, and animals were allowed to recover. A small decrease in the heart rate in response to phenylephrine (100 μl, 4 μg/kg) injected intravenously after bilateral aortic denervation, indicated successful denervation (Singewald et al 1997;Abdel-Rahman 1992). Following surgery, all animals (including CTRL group) were individually housed in Plexiglas cages (22 cm width, 45 cm length, 22 cm height).…”

“…Bilateral aortic denervation is an experimental animal model of neurogenic hypertension (Singewald et al 1997;Takeda et al 1989;Franchini and Krieger 1992;Kouvelas et al 2006). Thereby, the aortic depressor nerve is bilaterally transected, causing an almost complete disruption of baroreceptors and resulting in hypertension, accompanied by elevated blood pressure lability (Mauad et al 1992) and tachycardia (Singewald et al 1997;Takeda et al 1989). In a recent study by our group, the lack of blood pressure stimuli to the CNS, evoked by bilateral aortic denervation, leads to acute neuronal damage in brain areas known to be involved in memory and anxiety-like behaviour, such as hippocampus, amygdala, and the cortex (Kouvelas et al 2009).…”

Effects of inescapable shock and conditioned fear on the release of excitatory and inhibitory amino acids in the locus coeruleus

“…The vessel was sealed around the catheter by a vessel glue. Superfusion of the locus coeruleus was carried out as previously described (Singewald et al 1997;Kaehler et al 1999). Briefly, a guide cannula (outer diameter 0.9 mm, inner diameter 0.6 mm) was stereotaxically inserted under anaesthesia until the tip of the cannula was 2 mm above the locus coeruleus.…”