Stimulation of the hypothalamic defence area (HDA) in rats produces a cardiorespiratory response characterised by an increase of respiratory rate, tachycardia and a marked pressor response. The cardiovascular response is similar to that obtained during chemical stimulation of the A5 catecholaminergic region of the pons. We have demonstrated a functional interaction between these two regions inhibiting A5 neurones with muscimol (Dawid-Milner et al. 2001).
In order to characterise the role of glutamate in the cardiorespiratory response to HDA stimulation, experiments were carried out in spontaneously breathing anaesthetised rats (sodium pentobarbitone 60 mg kg-1 I.P., supplemented with 20 mg kg-1 I.V.). At the end of the experiments animals were humanely killed.
The cardiorespiratory response evoked by electrical stimulation of the HDA (1 ms pulses, 20-50 µA, given at 100 Hz, for 5 s) was analysed before and after the microinjection of kinurenic acid (5-10 nmol), MK-801 (1 pmol), MCPG (0.1 nmol) and CNQX (1 pmol) into the A5 region (50 nl, 5 s, in PBS pH 7.4 ± 0.1). All data were compared statistically using Student’s paired t test. Results are expressed as mean ± S.E.M.
The inhibition of glutamate receptors with the microinjection of kinurenic acid (n = 9) into the A5 region increased resting mean arterial pressure (P < 0.01). No changes were observed in resting respiratory frequency or heart rate. After the microinjection of kinurenic acid the pressor response and the tachycardia to HDA stimulation were diminished (36.7 ± 3.2 to 16.8 ± 2.6 mmHg P < 0.001; from 35.9 ± 4.4 to 11.2 ± 5.4 b.p.m., P < 0.001). No change in the respiratory response was observed.
No changes of cardiorespiratory parameters at rest were observed after the inhibition of NMDA receptors with the microinjection of MK-801 (n = 8) into the A5 region. No changes were observed in the cardiorespiratory response to HDA stimulation after the microinjection of MK-801 in A5 region.
The inhibition of non-NMDA receptors with CNQX (n = 8), or metabotropic receptors with MCPG (n = 8) increased resting mean arterial pressure (CNQX 105.1 ± 0.93 to 113.2 ± 2.5 mmHg, P < 0,01; MCPG from 104.2 ± 1.1 to 119.1 ± 1.6 mmHg, P < 0.01). No changes were observed in resting respiratory frequency or heart rate. The microinjection of CNQX or MCPG within the A5 region decreased the evoked tachycardia (CNQX from 29.7 ± 6.6 to -8.3 ± 10.6 b.p.m., P < 0.001; MCPG from 29.5 ± 4.3 to 11.5 ± 3.7 b.p.m., P < 0.01) to HDA stimulation. No changes were observed in the intensity of the pressor or tachypnoeic response.
These results suggest that the inhibition of A5 glutamate receptors decreases the tachycardia evoked on HDA stimulation. New data on the role of the A5 region in the control mechanisms of cardiorespiratory activity are also inferred.
This work was supported by the DGESIC PM99-0163, Spain.