Proceedings of The Physiological Society

University of Leeds (2002) J Physiol 544P, S019

Communications

Right atrial receptors inhibit renal sympathetic nerve activity via GABA interneurones in the PVN of rats

Z. Yang and J.H. Coote

Department of Physiology, University of Birmingham, Birmingham B15 2TT, UK


Stimulation of right atrial receptors in the rat reflexly reduces sympathetic nerve activity to the kidney (RSNA, Pyner et al. 2002). However, it is unclear whether the inhibitory effect on renal sympathetic vasomotor tone is mediated at the paraventricular nucleus (PVN) of the hypothalamus or at the spinal cord. Evidence has shown that endogenous nitric oxide (NO) within the PVN can inhibit RSNA (Zhang et al. 1997), an action mediated via GABA interneurones in PVN (Zhang & Patel, 1998). The present experiments were designed to test whether the volume reflex reduction in RSNA involves PVN or a spinal site or both. Thirteen Wistar rats, weighing 312.4 ± 5.7 g, were anaesthetised with urethane and chloralose and recordings were made of arterial blood pressure, heart rate and RSNA. A small inflatable balloon was inserted down the right superior vena cava to stretch the vein-atrial junction. A double-barrelled glass micropipette was placed stereotaxically in PVN, for microinjections of drugs. An intrathecal catheter was placed via the cisterna magna with its tip at T10. Drugs were applied intrathecally in a volume of 10 ml. Statistical analysis was performed using a Mann-Whitney U test, following a two-way repeated measure ANOVA. Results are expressed as means ± S.E.M. Rats were killed by overdose of urethane at the end of experiments. Atrial receptors stimulated by balloon inflation reduced RSNA by 28 ± 3.7 % without changing blood pressure. Microinjection of the GABAA receptor antagonist bicuculline (0.05 mM, 100 nl) into PVN increased RSNA by 63 ± 13 % and this was little changed when combined with balloon inflation (RSNA increased by 75 ± 16 %). Microinjection of NOS inhibitors L-NAME (0.1 mM, 100 nl) or L-NMMA (0.2 mM, 100 nl) into PVN elicited increases in RSNA of 36 ± 8 and 54 ± 10 %, respectively. These increases were prevented by balloon inflation, RSNA activity being 8 ± 8 and 2 ± 2 %, respectively, compared with baseline control (P ?le? 0.01). To rule out the possibility that the atrial reflex inhibition was in part dependent on PVN spinal projections shown to inhibit RSNA via spinal D1 receptor, a dopamine D1 receptor antagonist SCH23390 (0.05 mM) was intrathecally applied to the spinal cord. The effect of balloon inflation on RSNA was not significantly reduced. Furthermore intrathecal application of GABA receptor antagonist bicuculline (0.03 mM) had no significant effect on the reflex inhibition of RSNA. It was concluded that atrial receptor activation causes an inhibition of RSNA at the PVN and this effect is mediated by GABA.

This work was funded by The Wellcome Trust.

All procedures accord with current UK legislation.

Where applicable, experiments conform with Society ethical requirements