Proceedings of The Physiological Society

University of Cambridge (2004) J Physiol 555P, PC14


PVN-spinal oxytocin neurones selectively increase heart rate in the anaesthetised rat

Z. Yang*, M. Wheatley† and J.H. Coote‡

* The Medical School, University of Nankai, Tianjin, PR China, 300071, †School of Biosciences, The University of Birmingham, Birmingham B15 2TT and ‡Department of Physiology, The University of Birmingham, Birmingham B15 2TT, UK

In a previous study we showed that activation of spinally projecting neurones in the hypothalamic paraventricular nucleus (PVN) could increase sympathetic activity to the kidney via the release of vasopressin (Yang et al. 2002). There was no effect mediated by PVN-spinal oxytocin neurones despite these forming an almost equally abundant projection to the thoracic spinal cord (Cechetto et al. 1988). However an early study by Yashpal et al. (1987) had revealed that intrathecal (i.t.) application of oxytocin to the spinal cord preferentially increased heart rate. The present study was designed to determine if activation of PVN-spinal neurones could increase heart rate and whether oxytocin neurones were involved.

Eight Wistar rats were anaesthetised with urethane, chloralose mixture (650 mg kg-1, 50 mg kg-1) I.V. and a glass micropipette was inserted into PVN for microinjection of D,L-homocysteic acid (DLH) to activate neurones. Blood pressure and heart rate was recorded and the efficacy of spinal pathways tested by i.t. application of agonists and antagonists via a catheter inserted via the foramen magnum so that its tip lay at T3 segment. Statistical analysis was performed using Student's two tailed, paired t test. Rats were killed by overdose of urethane at end of experiment.

Oxytocin given i.t. (10 µl, 0.02 mM) increased heart rate by 26 ± 5 beats per min (b.p.m.) and this was significantly reduced to 5 ± 1 b.p.m. (P < 0.01) when preceded by a highly selective non-peptide oxytocin antagonist L368899 (Yang et al. 2002). Similar small increases of 34 ± 5 b.p.m. in heart rate were elicited from a number of sites in the PVN which were significantly reduced to 24 ± 5 b.p.m. (P < 0.05). At some of these sites heart rate increases were tested by i.t. application of the glutamate antagonist kynurenic acid (10 µl, 4.0 mM) and were effectively blocked (29 ± 4 b.p.m. before, 2 ± 3 b.p.m. after, P < 0.01). In contrast no PVN elicited heart rate increases were significantly changed by prior i.t. application of a vasopressin V1a antagonist (Yang et al. 2002) (10 µl, 0.05 mM). The PVN elicited heart rate increases were unaffected by bilateral vagotomy (22 ± 8 before, 22 ± 4 after, n = 4) but were completely blocked by I.V. β 1 adrenoreceptor esmolol (1 mg kg-1) (29 ± 4 before to 6 ± 2 after, n = 4), indicating they were sympathetically mediated.

The results indicate that some PVN-spinal oxytocin neurones may selectively innervate cardiac sympathetic neurones. In view of a previous study (Yang et al. 2002) showing a significant influence of PVN-spinal vasopressin neurones on vasomotor neurones to the kidney we suggest there may be a functional cardiovascular coding represented by these two sets of peptidergic neurones.

This work was supported by The British Heart Foundation

Where applicable, experiments conform with Society ethical requirements