Abstract 539: Reduced Firing Activity of Afferent Renal Innervation in the 2kidney/1clip Model of Hypertension

Abstract

Introduction: Renal denervation has been shown to be effective in patients with hypertension. Recently, we found that afferent renal neurons show a distinctive feature, exhibiting predominantly a sustained firing upon current injection due to a specific expression of TTX resistant Na-channels. So far, the activity of these specific sensory neurons in hypertension is unclear. Hence we wanted to test the hypothesis that the firing pattern of renal afferent neurons is altered in the 2K/1C model of hypertension. Methods: Hypertension was induced by unilateral clipping of the renal artery in Sprague Dawley rats 3 weeks prior to experiments. Blood pressure was confirmed by an intraarterial measurement. Retrograde labelling (DiI) allowed the identification of renal afferent neurons in the Dorsal root ganglion (DRG Th11-L2). Current clamp was used to characterize neurons as “tonic”, i.e. sustained action potential (AP) firing or “phasic”, i.e. <5 APs according to their firing upon current injections. Electrophysiological parameters and AP properties were determined in neurons of hypertensive animals and controls. Renal morphology was investigated. Results: Renal DRG neurons of hypertensive animals (n=88) showed a significant decrease in tonic firing pattern compared to controls (n=84) (44.3% [39/88] vs. 59.5% [50/84], p< 0.05). Current Clamp analysis revealed no significant change in action potential shape in hypertensive animals (overshoot, firing threshold, AP- duration). Tonic cells revealed a higher capacity in hypertensive rats (124pF vs. 87.8pF, p<0.01), all other parameters (resting potential, resistances) were equal in both groups. No differences in renal pathomorphology could be observed between clipped and non-clipped kidney in hypertensive animals. (BP: 187.5 mmHg versus controls: 106.5mmHg) Conclusion: Hence the excitability of afferent renal neurons in a model of renovascular hypertension is significantly altered, as renal afferent DRG neurons exhibit less sustained firing upon stimulation. Sustained high blood pressure is possibly rather characterized by a generally decreased afferent renal activity with impaired sympathoinhibition than by activated sympathoexcitatory fibers from the clipped kidney.