Submitted on June 11, 2007
Accepted on June 29, 2007
Renal sympathetic nerves modulate erythropoietin plasma levels after transient hemorrhage in rats
Tilmann Ditting1, Karl F. Hilgers1, Alexander Stetter2, Peter Linz1, Christina Schonweiss3, and Roland Veelken4*
1 Medicine-Nephrology, University of Erlangen-Nurnberg, Erlangen, Germany
2 Bohringer-Mannheim, Mannheim, Germany
3 Medicine-Nephrology, University of Erlangen-Nurnberg, Erlangen, Bavaria, Germany
4 Medicine-Nephrology, University of Erlangen-Nuremberg, Erlangen, Bavaria, Germany
* To whom correspondence should be addressed. E-mail: mfm431{at}rzmail.uni-erlangen.de.
Objective: In contrast to other sympathetic tracts renal sympathetic nerve activity (RSNA) decreases during hypotensive hemorrhage. The significance of this "paradox" is unknown. We tested the hypothesis that RSNA modulates renal perfusion and thus erythropoietin (EPO) release after transient hypotensive hemorrhage (tr-hHem) in anesthetized rats.
Methods: EPO was measured before and after 30 minutes of tr-hHem (i.e., -40 mmHg from mean baseline blood pressure (MAP), followed by reinfusion of blood) and 120 minutes thereafter in sham-denervated rats, after renal denervation (DNX) or bilateral cervical vagotomy (VX) to blunt the RSNA decrease mediated by a cardiopulmonary reflex. RSNA, renal Doppler flow (DOP), renal vascular resistance (RVR), resistance index (RI), oxygen delivery/uptake (DO2/VO2) were measured.
Results: RSNA decreased in intact animals (-40±5% from baseline p<0.05). This was blunted by VX. With innervation EPO level remained stable. In DNX rats EPO was increased at minute 120 (49±3 vs.74±2 mU/ml; p<0.05), in VX-rats this (47±2 vs. 62±4 mU/ml; p<0.05) was less pronounced.
DO2 in DNX rats was lower compared to intact and VX (0,25±0,04 vs. 0,51±0,06 and 0,54±0,05 mlO2/min; p<0,05) due to lower DOP and increased RVR. RVR and DO2 were similar in intact and VX, but RI differed between all groups (0,70±0,02 vs. 0,78±0,02 vs.0,85±0.02; p<0,05 intact vs. VX vs DNX) indicating differential reactivity of renal vasculature. VO2 was unaffected by VX and DNX.
Conclusions: Renal sympathoinhibition during hypotensive hemorrhage might help to preserve sufficient oxygenation of renal tissue by modulation of hemodynamic mechanisms that act to adapt renal oxygen availability to demand.
