Abstract
Objective: Afferent renal nerves exhibit a dual function. They influence intrarenal immunological processes by release of neurokinins like CGRP and control central sympathetic outflow via afferent electrical activity. The former seems to be important in renal inflammation whereas the sympathetic modulation by afferent electrical activity is not fully understood in cardiovascular disease and hypertension. Hence, we hypothesized that augmented effects of CGRP in renal inflammation occur with increased afferent renal nerve activity. Design and Method: As inflammatory model, normotensive renal inflammation (RI) was induced by i.v. injection of 1.75 mg/kg BW OX-7 antibody to rats to avoid confounding blood pressure effects by choosing a hypertensive model in the first place. Animals were investigated neurophysiologically and pathomorphologically using standard techniques 6 days after RI induction. Results: Blood pressure (BP) was normal, hence confounding BP effects were unlikely. RI rats exhibited albuminuria (61 ± 6 μg/24 h), infiltration of macrophages in the interstitium (26 ± 4 cells/hp field) and glomeruli (3.7 ± 0.6 cells/glomerular X-section). Pretreatment with the CGRP antagonist rCGRP 8-37 (15 nmol/kg) significantly reduced proteinuria and macrophage infiltration suggesting increased activity of CGRP. In an in-vitro assay, renal RI tissue exhibited increased CGRP release (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 CGRP. 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 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). Conclusions: In contrast to our hypothesis increased release of neurogenic CGRP aggravating RI occurred with decreased ARNA. Increased RSNA pointed to a reduced tonic inhibition by ARNA. The latter mechanism might worsen sympathetic dysregulation and renal damage as in hypertension.
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