Afferent peptidergic renal nerves exhibit a dual function. They influence intrarenal immunological processes by releasing peptides like CGRP and control central sympathetic outflow via afferent electrical activity. The former seems to be important in renal inflammation whereas the modulation of sympathetic outflow by afferent electrical activity is not fully understood. Hence, we wanted to test the hypothesis that augmented effects of CGRP in renal inflammation occur with increased afferent renal nerve activity.
As inflammatory model, normotensive renal inflammation (RI) was induced by i.v. injection of 1.75 mg/kg BW OX-7 antibody to rats. Animals were investigated neurophysiologically and pathomorphologically using standard techniques at day 6 after induction of RI.
There was no increase in blood pressure (BP) in RI animals, hence confounding effects of BP were unlikely. RI rats exhibited albuminuria (61±6 μg/24h), infiltration of macrophages in the interstitium (26 ± 4 cells/high-power field) and glomeruli (3.7±0.6 cells/glomerular cross-section). Pretreatment with the CGRP antagonist rCGRP 8-37 (Tocris Bioscience 15nmol/kg) significantly reduced proteinuria and macrophage infiltration suggesting increased activity of CGRP in RI. In an in-vitro assay, renal tissue of rats with RI exhibited increased release of CGRP (14 ± 3 pg/ml vs. controls 6.8 ± 2.8 pg/ml; p<0.05, n=8). RI tissue from renally denervated rats showed no detectable levels of CGRP. These results suggested CGRP release from renal nerves at a higher rate in RI. Directly recorded afferent renal nerve activity (ARNA; spikes/sec) was unexpectedly lower in RI compared to controls (8.0 ± 1.8 vs. 27.4 ± 4.1 Hz*,n=6, p<0.05). On the other hand, the burst-frequency of directly recorded renal sympathetic nerve activity (RSNA) in RI was significantly higher than in controls (14.7 ± 0.9 vs. 11.5 ± 0.9 bursts/sec*; n=6, *p<0.05).
In contrast to our assumption increased release of neurogenic CGRP aggravating renal inflammation occurred with decreased ARNA. Increased RSNA pointed to a reduced tonic inhibition by ARNA. In hypertension, the later mechanism might worsen sympathetic dysregulation and renal damage.