Abstract
AimIt is well-established that angiotensin II exerts a dampening effect on the baroreflex within the nucleus tractus solitarii (NTS), the principal brainstem site for termination of baroreceptor afferents and which is densely populated with gamma-aminobutyric acid (GABA)ergic neurons and nerve terminals. The present study was designed to investigate whether local release of GABA is involved in the effects mediated by local angiotensin II within the NTS.MethodsIn vivo microdialysis was used for measurement of extracellular glutamate and GABA levels and for infusion of angiotensin II within the NTS of conscious normotensive Wistar rats. The mean arterial pressure (MAP) and heart rate response to local infusion of angiotensin II were subsequently monitored with a pressure transducer under anesthesia. The angiotensin II type 1 receptor (AT1R) antagonist, candesartan, was used to assess whether responses were AT1R dependent and the nitric oxide (NO) synthase inhibitor, N(ω)-nitro-L-arginine methyl ester (L-NAME), was used to assess the involvement of NO in the evoked responses by infusion of angiotensin II. The MAP and heart rate responses were monitored with a pressure transducer.ResultsLocal infusion into the NTS of angiotensin II induced a significant to ninefold significantly increase in extracellular GABA levels; as well as MAP was increased by 15 mmHg. These responses were both abolished by co-infusion of either, the angiotensin II type 1 receptor antagonist, candesartan, or the NO synthase inhibitor, L-NAME, demonstrating that the effect is not only AT1R dependent but also NO dependent. The pressor response to angiotensin II was reversed by co-infusion with the GABAA receptor antagonist, bicuculline. Local blockade of NO synthase decreased both, GABA and glutamate concentrations.ConclusionOur results suggest that the AT1R mediated hypertensive response to angiotensin II within the NTS in normotensive rats is GABA and NO dependent. Nitric oxide produced within the NTS tonically potentiates local GABA and glutamate release.
Highlights
The central nervous system network that regulates the level of sympathetic tone and, blood pressure, is located in the brainstem and consists mainly of the rostral ventrolateral medulla (RVLM), the paraventricular nucleus (PVN) of the hypothalamus and the nucleus tractus solitarii (NTS) (Guyenet, 2006)
As angiotensin II (Ang II) and gamma-aminobutyric acid (GABA) are both known to interact with nitric oxide (NO) in other brain area’s (Dupont and Brouwers, 2010), and as NO was suggested to be involved in the Ang II mediated modulation of the baroreceptor reflex pathway (Paton et al, 2001a), we aimed to investigate the possible role of the NO-pathway in the responses evoked by angiotensin II type 1 receptor (AT1R) activation within the NTS
In a first series of experiments we investigated the effect of local Ang II infusion in two different doses (1 or 3 μg μL−1 h−1) within the NTS on extracellular glutamate (Figure 2A) and GABA (Figure 2B) levels
Summary
The central nervous system network that regulates the level of sympathetic tone and, blood pressure, is located in the brainstem and consists mainly of the rostral ventrolateral medulla (RVLM), the paraventricular nucleus (PVN) of the hypothalamus and the nucleus tractus solitarii (NTS) (Guyenet, 2006). It is well-established that the RVLM, the so-called brainstem ‘pressor area,’ is a key site for the regulation of sympathetic tone and blood pressure (Dupont and Brouwers, 2010). Baroreceptor mediated activation of NTS neurons indirectly inhibits the RVLM through activation of GABAergic neurons of the CVLM, resulting in a reduced sympathetic outflow with blood pressure and heart rate (HR) reduction (Guyenet, 2006)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
