Renal Sympathetic Denervation as a Model for Studying the Influence of Hyperoxygenation and Low Salt Intake on Sympathetic Activity and Blood Pressure

Renal sympathetic denervation (RSD) has emerged as an attractive minimally
invasive treatment option for patients with therapy resistant hypertension.
Despite its general effectiveness, the blood pressure (BP) lowering effect of
RSD is highly variable and incompletely understood. Radiofrequency ablation of
the renal sympathetic nerves in RSD non-selectively targets both efferent and
afferent renal sympathetic nerve fibers. Reducing efferent sympathetic outflow
to the kidneys may decrease renin release and tubular sodium retention, while
increasing renal blood flow. Contra-directionally, interruption of afferent
renal nerve traffic through RSD may lower central sympathetic nerve activity
(SNA) by attenuation of the renal stimulatory actions on central SNA. Mounting
evidence suggests that the driving force behind afferent renal sympathetic
nervous activation is renal medullary hypoxia, determined by the balance
between renal oxygen supply and demand. Accordingly, supplementation of 100%
oxygen in CKD patients has shown to decrease SNA. Since sodium transport is the
primary oxygen consuming activity of the kidneys, renal medullary hypoxia and
thus renal afferent sympathetic nerve activity may be affected by dietary
sodium intake. Indeed, it has been shown that lowering dietary sodium intake
increases medullary oxygenation reduces SNA. Finally, SNA itself may exaggerate
renal medullary hypoxia, since increased sympathetic outflow attenuates renal
blood flow, but simultaneously increase tubular oxygen demand through increased
sodium retention. Altogether this yields a vicious circle of medullar hypoxia
leading to sympathetic hyperactivity and vice versa, amplified by increased
dietary sodium intake.
We hypothesize that through its efferent effects, with inhibition of renin
release and tubular sodium retention, RSD may potentiate the BP lowering effect
of a dietary sodium restriction.
Additionally, we hypothesize that supplementation of 100% oxygen has a less
profound effect on SNA during dietary sodium restriction and we expect the
effect of oxygen supplementation on SNA to be blunted after RSD from reduced
renal afferent signaling.

To study the effects of renal denervation on the responsiviness of blood
pressure to sodium and hyperoxigenation, respectively.

A prospective clinical cohort study with invasive measurements before and after
RSD.

The dietary salt restriction of one week as proposed in this study is not
associated with any substantial risk. The hemodynamic measurements are all
non-invasive and can be carried out safely. Supplementation of 100% oxygen
10L/min during 10 minutes using a non-rebreathing mask does not propose a risk
for participating patients. There is no individual but only a group related
benefit for participation in this study.