Some hypothalamic paraventricular (PVN) parvocellular neurones either project to spinally projecting neurones in the rostral ventrolateral medulla (RVLM) or to sympathetic preganglionic neurones in the spinal cord or to both (Pyner & Coote, 2000). In the present study the functional influence of the PVN-spinal projection was tested by examining blood pressure (BP) and renal sympathetic nerve activity (RSNA) responses to PVN stimulation (D,L-homocysteic acid, DLH 0.2 M) in the presence and absence of RVLM-spinal influences.

Fourteen Wistar rats were anaesthetised with urethane and chloralose and a glass micropipette was inserted into PVN for microinjection of DLH. A double-barrelled glass micropipette was placed into the area of RVLM for microinjection of drugs. Change in the efficacy of spinal pathways was tested by intrathecal (I.T.) application of drugs via a catheter inserted via the foramen magnum so that its tip lay at T10. Statistical analysis was performed using Student’s two-tailed, paired t test. Rats were killed by overdose of urethane anaesthetic at the end of experiment.

After identifying an excitatory site in the PVN on the left side, a micropipette was stereotaxically positioned in the ventral medulla on both sides and the rostral ventrolateral vasomotor area identified by microinjection of glutamate (1 nmol). A number of control BP and RSNA responses were then recorded following which the GABA agonist muscimol (200 pmol) was microinjected into both left and right RVLM. Muscimol caused a small fall in BP from 72.4 ± 3.7 mmHg to 68.8 ± 3.4 mmHg (means ± S.D.; NS); reduced RSNA from 13.3 ± 1.6 Hz to 11.8 ± 1.7 Hz, P < 0.002) and abolished a baroreflex inhibition of RSNA induced by pressor response to phenylephrine I.V. (4-6 µg). However bilateral muscimol into RVLM did not reduce the BP increase in response to PVN stimulation (9.2 ± 1.1 mmHg before, 12.6 ± 2.5 mmHg after) or the increase in RSNA (69.4 ± 13.1 % before, 62.9 ± 13.9 % after). Intrathecal application of the glutamate antagonist kynurenic acid (10 µl, 4 mM, Sigma) after muscimol block of RVLM, reduced the PVN-BP response from 14.7 ± 3.1 mmHg to 7 ± 1.4 mmHg (P < 0.07) and the PVN-RSNA response from 55.9 ± 13.5 % to 35.8 ± 12.1 % (P ²le³ 0.05). The PVN sympathoexcitation were also reduced by I.T. V1a antagonist (10 µl, 0.05 mM, Sigma), BP from 18.9 ± 3.8 mmHg to 12.9 ± 2.4 mmHg (P ²le³ 0.2) and RSNA from 48.6 ± 10 % to 38.5 ± 8.8 % (P = 0.1).

The results indicate that PVN-spinal neurones can act independently of RVL to increase sympathetic vasomotor activity and that glutamate or vasopressin neurones may contribute to this effect.

This work was funded by The Wellcome Trust.