Decrease in afferent evoked glutamate release in the rat NTS in chronic heart failure

Homeostatic mechanisms maintain arterial blood pressure, blood volume and arterial blood gases within a narrow physiological range. One of the important sites in the brain involved in this regulation is the nucleus tractus solitarii (NTS) which receives afferent information from baroreceptors, cardiopulmonary and chemoreceptors. The major transmitter involved is considered to be glutamate (Baude et al 2009, J Chem Neuroanat 38, 145–153), which is released into the NTS when these cardiovascular/visceral afferents are activated. The present study was carried to determine if this release of glutamate from cardiovascular afferents can be detected using glutamate biosensors (Sarissaprobes®) and whether it is altered in heart failure. Heart failure was induced under anaesthesia by ligation of the coronary artery (Pfeffer et al., 1979, Circ Res. 44:503–512). Rats with chronic heart failure (5–6 weeks post‐infarction; infarct size between 30–40 %) or sham‐operated were then anaesthetized with α‐chloralose (100 mg/kg; i.v), neuromuscular blocked and artificially ventilated and the biosensor placed in the NTS. Cardiopulmonary afferents were activated by phenylbiguanide (PBG; 20μg per animal i.a.) and the depressor reflex (baroreceptor activation) by i.v. injection of norepinephrine (0.5 μg/kg). Cardiopulmonary and depressor reflex activation in sham‐operated rats caused a detected release of glutamate in the NTS of 2.6 ± 0.8 μM (n=10) and 1.1 ± 0.2 μM (n=10) respectively. In the case of cardiopulmonary reflex, this was associated with a decrease in MAP of 42 ± 7 mmHg and HR of 99 ± 20 bpm, while for the depressor reflex there was an increase in MAP of 37 ± 5 mmHg and a decrease in HR of 21 ± 8 bpm. In rats with heart failure, although there was no significant difference in the cardiovascular effects caused by activation of these reflexes, the amount of glutamate detected was significantly (P<0.001) reduced to 0.5 ± 0.3 μM (n=6) and 0.2 ± 0.1 μM (n=6) respectively. Resting MAP and HR were similar in both groups. Thus in heart failure there is an approximate reduction of 80% in the glutamate being released by these afferents. This large decrease in the amount of detected glutamate overflow within the NTS in chronic heart failure could indicate a reduction in “spare capacity” in such transmission, although there is still enough to enable a “normal” reflex responses. It is possible that other transmitters may have also come into play to help maintain these reflexes in heart failure. Support or Funding Information British Heart Foundation project grant No PG/13/79/30429