Role of GABA and NO in the paraventricular nucleus-mediated reflex inhibition of renal sympathetic nerve activity following stimulation of right atrial receptors in the rat

The aim of this study was to determine the site within the brain at which inhibition of renal sympathetic nerve activity (RSNA) occurs following right atrial receptor stimulation. The atrial receptors were stimulated by inflating a balloon at the right vena cava-atrium junction and the reflex effect was observed before and during application of neurotransmitter agonists and antagonists into the paraventricular nucleus (PVN), or intrathecally to the spinal cord. Balloon inflation reduced RSNA by 29.1 +/- 3% without changing blood pressure in anaesthetised Wistar rats. Microinjection of the GABA, receptor antagonist bicuculline (0.025 mm, 100 nl) into the PVN increased RSNA by 42.3 +/- 5% and this was changed little by balloon inflation when PVN increased RSNA by 50.6 +/- 6.3%. Microinjection of the nitric oxide synthase (NOS) inhibitors L-NAME (0.1 mm, 100 nl) or L-NMNIA (0.2 mm, 100 nl) into PVN elicited increases in RSNA of 36 +/- 8% or 54 +/- 10%, respectively. Balloon inflation during PVN stimulation plus NOS inhibition resulted in RSNA activity of 8 +/- 4% or -1 +/- 1%, respectively, compared to baseline control. Baseline RSNA was similar throughout this series of tests ranging from 9.1 +/- 1.3 to 11.5 +/- 1.1 spike counts s(-1). To rule out the possibility that the atrial reflex inhibition was in part dependent on a dopamine-mediated PVN-spinal projection pathway inhibiting RSNA at a spinal locus, a dopamine D1 receptor antagonist SCH 23390 was intrathecally applied to the spinal cord. The effect of subsequent balloon inflation on RSNA was not significantly reduced. It was concluded that atrial receptor activation causes an inhibition of RSNA at the PVN and that this effect is mediated by GABA.