Hypothalamic defence area (HDA) activation produces a cardiorespiratory response characterised by tachypnoea with inspiratory facilitation, hypertension and tachycardia. The response is similar to that evoked during stimulation of lateral parabrachial nucleus (lPB) of the pons (Lara et al. 2002).
To characterise the role of glutamate in the cardiorespiratory response evoked by HDA stimulation, experiments were carried out in spontaneously breathing rats anaesthetised with sodium pentobarbitone (60 mg kg-1 I.P., supplemented as necessary 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 µA, given at 100 Hz, over 5 s) was analysed before and after the microinjection of kynurenic acid (KA, 5 nmol), MK-801 (1 pmol) and CNQX (1 pmol) into both lPB and medial parabrachial nucleus (mPB) (50 nl over 5 s, pH 7, 4 ± 0.1 in phosphate-buffered saline). All data were compared statistically using Student’s paired t test. Results are expressed as means ± S.E.M.
Inhibition of glutamate receptors with the microinjection of KA in lPB (n = 7) increased blood pressure and heart rate (from 105.1 ± 3.6 to 120.3 ± 2.8 mmHg, P < 0.001; from 339.8 ± 10.9 to 368.2 ± 10.2 b.p.m., P > 0.001); no changes were observed in respiratory rate. After KA microinjection the respiratory response to HDA stimulation was abolished; the pressure response and tachycardia were diminished (from 33.7 ± 10.9 to 6.8 ± 10.1 mmHg, P < 0.001; from 27.7 ± 10.4 to -0.05 ± 10.6 b.p.m., P < 0.001). KA was also microinjected in mPB (n = 8). After the injection of KA the pressure response and tachycardia to HDA stimulation were diminished (from 38.5 ± 7.6 to 16.7 ± 11.2 mmHg P < 0.001; from 27.4 ± 12 to -0.3 ± 14.2 b.p.m., P > 0.001) whilst no changes were observed in the respiratory response.
The inhibition of NMDA receptors with MK-801 (n = 8) or non-NMDA receptors with CNQX (n = 8) microinjected into both lPB and mPB increased arterial pressure and heart rate (lPB MK-801 from 108.4 ± 2.1 to 125.7 ± 2.4 mmHg, P < 0.01, and from 320.2 ± 14.5 to 371.9 ± 9.8 b.p.m., P < 0.01; lPB CNQX from 106.1 ± 1.6 to 118.5 ± 1.6 mmHg, P < 0.01, and from 352.4 ± 8.4 to 400.4 ± 12.8 b.p.m., P < 0.01); no changes were observed in respiratory frequency. MK-801 or CNQX within either lPB or mPB decreased the evoked tachycardia and the pressure response to HDA (PBl MK-801 from 41 ± 3.6 to 26.3 ± 5.3 mmHg P < 0.001, and from 36.9 ± 12.2 to 8.1 ± 13.4 b.p.m., P < 0.01; PBl CNQX from 40.3 ± 9.7 to 28.2 ± 10.3 mmHg, P < 0.01, and from 36.4 ± 12.4 to -1.1 ± 13.8 b.p.m., P < 0.001; PBm MK-801 from 37.4 ± 11.8 to 26.5 ± 10.4 mmHg, P < 0.05; PBm CNQX from 39.2 ± 8.2 to 25.3 ± 10.2 mmHg, P < 0.01, and from 49.4 ± 9.6 to 31.1 ± 13.8 b.p.m., P < 0.01); no changes were observed in the intensity of the respiratory response.
These results suggest the importance of PB neurones modulating the cardiorespiratory response to HDA activation. Inhibition of lPB glutamate receptors (KA) abolished the classic tachypnoea evoked from HDA. The hypertension and tachycardia evoked from HDA were attenuated after specific inhibition of glutamate receptors (KA), NMDA receptors (MK-801) and non-NMDA receptors (CNQX) into either lPB or mPB neurones.
This work was supported by the DGESIC PM99-0163, Spain.