Proceedings of The Physiological Society

Kings College London (2005) J Physiol 565P, PC168

Communications

Intracarotid hypertonic saline activates PVN and sympathetic neurones by a PVN spinal pathway in anesthetised rats

Coote, John H.; Yang, Zhuo ;

1. Medical College,University of Nankai, TianJin, China. 2. Division of Biomedicine, University of Birmingham, Birmingham, United Kingdom.


Previous studies have shown that orthograde injection of hypertonic saline into one carotid artery can activate neurones in the organum vasculosum lamina terminalis (OVLT) which in turn excites parvocellular neurones in the paraventricular nucleus of the hypothalamus (PVN) and thus may effect neurones influencing arterial blood pressure (Chen & Toney, 2001). In the present study we sought to show that the osmotic stimulus also activates sympathetic neurones to the kidney and to determine whether this is via a PVN spinal pathway. In 10 Wistar rats anesthetised with urethane, chloralose mixture (650 mg kg-1, 50 mg kg-1) i.v., a catheter was placed orthogradely in the right carotid artery for injection of hypertonic saline (1.7 M, 0.1 ml NaCl) and normal saline (0.9% NaCl) as a control. Arterial blood pressure (BP) and heart rate (HR) were monitored and renal sympathetic nerve activity (RSNA) was recorded from a renal nerve exposed retroperitoneally on the left side. 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. The animal was placed in a stereotaxic frame and a glass micropipette was positioned in the PVN for injection of drugs. Statistical analysis was performed using a two-tailed, paired Student's t test. Rats were killed by overdose of urethane anaesthetic at the end of the experiment. Intracarotid injection of NaCl significantly increased RSNA by 48.9 ±6.1% (p<0.05). HR was significantly decreased by -36.1±1.4 b.p.m. (p<0.05). BP was little changed (3.3±0.8 mm Hg). This action of NaCl was virtually abolished by prior microinjection of the glutamate receptor antagonist kynurenic acid (4mM, 100 nl) into RSNA exciting sites in the PVN (RSNA 5.9±2%,p<0.01; BP no change; HR decreased by -5.9±2.1 b.p.m., p<0.05). Spinal kynurenic acid (4mM, 10μl, i.t.) also reduced the RSNA response to intracarotid NaCl to 10.9±61.% (p<0.01), BP 0.8±0.9% (ns) and HR -16.5±4.5 b.p.m., p≤0.05, (n=7). Similarly i.t. application of V1a antagonist ((β-mercapto-β,β-cyclopentamethylenepropionyl1,-O-Et-Tyr2, Val4, Arg8) vasopressin, Sigma, 0.05mM, 10μl) before NaCl virtually abolished all the changes (RSNA 2.6±5.7%, BP 1.5±0.6 mm Hg, HR -7.8±2.2 b.p.m., p<0.01, n=9). From these data we suggest that osmoreceptor stimulation in the forebrain mediates cardiovascular changes via a glutamate dependent synapse in the PVN which then activates glutamate and vasopressin neurones projecting to spinal sympathetic neurones.

Where applicable, experiments conform with Society ethical requirements