Cardiac sympatho-excitatory action of PVN-spinal oxytocin neurones

Abstract

A significant proportion of the spinally projecting neurones in the paraventricular nucleus are immunoreactive for oxytocin. Some of these oxytocin neurones terminate on sympathetic preganglionic neurones in the upper thoracic spinal cord, a region from which cardiac sympathetic neurones originate. No studies have so far identified a cardiac action of the supraspinal oxytocin neurones. The present study was designed to test the hypothesis that these oxytocin neurones excite spinal cardiac sympathetic neurones. This was done by measuring heart rate changes in response to intrathecal oxytocin and a selective agonist, and to stimulation of paraventricular neurones before and during blockade of spinal sites with selective antagonists. Rats were anaesthetised with chloralose and urethane (50 mg and 650 mg/kg) and recordings were made of heart rate and blood pressure. Drugs in a volume of 10 µl were applied to the upper thoracic spinal cord via a catheter placed intrathecally with its tip at T2. The paraventricular nucleus was explored with a glass micropipette, placed stereotaxically, and filled with d, l-homocysteic acid (DLH, 200 mM) for exciting neurones and pontamine sky blue for marking the position. Oxytocin (0.002 mM) applied to the spinal cord elicited increases in heart rate (26 ± 5 beats per minute). This was mimicked by a highly selective oxytocin agonist. These heart rate increases were blocked selectively by two different oxytocin antagonists but unaffected by a V 1a vasopressin antagonist. Excitation of sites in dorsal and medial parvocellular sub-nuclei of the paraventricular nucleus elicited increases in heart rate (36 ± 3 bpm) which were significantly reduced by oxytocin antagonists but not affected by V 1a antagonist. Also these induced increases in heart rate were unaffected by vagotomy or i.v. atropine but were abolished by i.v. esmolol. It is concluded that there is a population of paraventricular-spinal oxytocin neurones that excite cardiac sympathetic preganglionic neurones controlling heart rate.