Renal sympathetic nerves modulate erythropoietin plasma levels after transient hemorrhage in rats

Abstract

In contrast to other sympathetic outflow tracts, renal sympathetic nerve activity (RSNA) decreases in response to hypotensive hemorrhage. The functional significance of this "paradox" is not known. We tested the hypothesis that RSNA modulates renal perfusion and thus erythropoietin (EPO) release after transient hypotensive hemorrhage in anesthetized rats. Plasma EPO was measured before and after 30 min of transient hypotensive hemorrhage (i.e., -40 mmHg from mean baseline blood pressure, followed by reinfusion of shed blood) and 120 min thereafter in sham-denervated rats, and after renal denervation (DNX) or bilateral cervical vagotomy (VX) to abolish/blunt the RSNA decrease mediated by a cardiopulmonary reflex. RSNA, renal Doppler flow, renal vascular resistance (RVR), resistance index, and oxygen delivery/uptake (Do(2)/Vo(2)) were measured. RSNA decreased in intact animals (-40 +/- 5% from baseline, P < 0.05). This was blunted by VX. With intact nerves, EPO level did not increase. 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. Do(2) in DNX rats was lower compared with intact and VX rats (0.25 +/- 0.04 vs. 0.51 +/- 0.06 and 0.54 +/- 0.05 ml O(2)/min; P < 0.05) due to lower Doppler flow and increased RVR. RVR and Do(2) were similar in intact and VX rats, but resistance index 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. Vo(2) was unaffected by VX and DNX. 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.

Renal nerve stimulation leads to the activation of the Na+/H+exchanger isoform 3 via angiotensin II type I receptor

“…All responses mediated by ESRN were completely abolished by a losartan-mediated AT1 receptor blockade. Taken together, our results demonstrate that higher NHE3-mediated proximal tubular sodium reabsorption induced by ESRN occurs via intrarenal renin angiotensin system activation and triggering of the AT1 receptor/inhibitory G-protein signaling pathway, which leads to inhibition of cAMP formation and reduction of PKA activity.sympathetic nervous system; ANG II; AT1 receptor and NHE3 THE IMPORTANCE OF THE renal nerve in regulating extracellular volume has been reported in different physiological and pathophysiological conditions (17,20,26,52,60). It has been postulated that the renal nerve serves as a link between the kidneys and the central nervous system (19).…”

“…sympathetic nervous system; ANG II; AT1 receptor and NHE3 THE IMPORTANCE OF THE renal nerve in regulating extracellular volume has been reported in different physiological and pathophysiological conditions (17,20,26,52,60). It has been postulated that the renal nerve serves as a link between the kidneys and the central nervous system (19).…”

Renal Denervation in Moderate to Severe CKD

“…30 In this context, it is noteworthy that data from both experimental and human studies have suggested a role of renal sympathetic nerves in the modulation of erythropoiesis. 31,32 There was a trend toward reduction of urinary albumin excretion after renal denervation, which may represent additional beneficial effects of direct sympathetic modulation beyond BP reduction alone. 9,19,33 We also observed a trend toward reduction in plasma circulating BNP concentrations after renal denervation.…”

The hypoxia inducible factor/erythropoietin (EPO)/EPO receptor pathway is disturbed in a rat model of chronic kidney disease related anemia

“…Serum EPO levels were also not increased in the bleeding experiment ( Table 2 ). This may be due to additional factors controlling EPO synthesis in the rat, including the sympathetic nervous system [ 24 ].…”