Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCB002

Poster Communications

Low-pressure baroreflex control of renal sympathetic nerve activity in rats exposed to chronic intermittent hypoxia: Effect of TRPV1 channel blockade.

S. AlMarabeh1, E. F. Lucking1, K. D. O'Halloran1, M. Abdulla1

1. Department of Physiology, University College Cork, Cork, Ireland.

Ischemic kidney is associated with sympathetic over-activity and impaired baroreflex control of blood pressure. Kidney hypoxia is observed in the chronic intermittent hypoxia (CIH)-induced hypertension model. This study investigated the baroreceptor reflex in a CIH rat model and whether renal transient receptor potential vanilloid 1 (TRPV1) contributes to the modulation of low-pressure baroreceptor reflex regulation of renal sympathetic nerve activity (RSNA). Wistar rats (225-272g) were exposed to CIH (90s exposure to 5% O2 followed by 210s exposure to 21% O2, 8 hr/day, n=4) or to normoxia (sham, 21% O2, n=4) for 14 days. On day 15, the rat was anaesthetized (induction: urethane, α-chloralose and sodium pentobarbitone mixture i.p. (416, 27 and 33mg/kg), maintenance: urethane and α-chloralose mixture (62 and 4mg/kg i.p.). Cannulae were inserted into the femoral artery to measure mean arterial pressure (MAP) and, heart rate (HR), and femoral vein to infuse saline (3ml/hr). The right kidney was exposed, renal nerves were dissected and held on bi-polar electrodes to record RSNA. After a 90min stabilization, the low-pressure baroreflex was studied by two consecutive volume expansion (VE) trials. In control conditions, rats received intrarenal infusion of saline (1ml/hr) 30min before and during VE (0.25ml saline/100g body weight/min for 30min i.v.). During test conditions, a TRPV1 blocker, capsazepine (CPZ) was infused (5µg/ml/hr) 30min before and during a repeat VE trial. RSNA sympatho-inhibitory response curves to VE were obtained from control and test conditions in sham and CIH rats. Rats were euthanized and the left kidney was harvested for histological assessment using hematoxylin and eosin stain. Values are mean±S.D. No major histological changes were revealed. Glomerular tuft area was equivalent between sham (7332±1628µm2, n=3) and CIH rats (7492±1531µm2, n=5; p=0.533, Mann Whitney test) when normalized to body weight. Basal MAP (102±13 vs. 99±7mmHg) and RSNA (0.73±0.18 vs. 0.93±0.47µV.s) were similar in sham and CIH groups, but HR (414±6 vs. 471±36bpm, p<0.05) was higher in CIH rats. VE decreased RSNA over the 30min period from baseline in sham rats and to a lesser extent in CIH rats (p=0.055, repeated measures two way ANOVA). In addition, area under the curve (AUC) for the sympatho-inhibition during VE was smaller in the CIH compared with the sham group (498±284 vs. 1308±819, p=0.05, one tailed independent t-test). CPZ had no effect on the sympatho-inhibitory response to VE in sham and CIH rats (AUC, Sham: Saline vs. CPZ, 1308±819 vs. 1526±642; CIH: 498±284 vs. 690 ±637). Preliminary findings suggest that moderate exposure to CIH does not induce pathological changes in the kidney but blunts low-pressure baroreflex control of RSNA through a mechanism that might not involve renal afferent TRPV1.

Where applicable, experiments conform with Society ethical requirements