Abstract 117: Renal Nerves Mediate Renal Inflammatory Signaling Independent of Hypertension in the DOCA-salt Rat

Abstract

Preclinical and clinical studies demonstrate renal denervation (RDx) may be an effective treatment for hypertension (HTN); however, the mechanisms of this effect remain unknown. We recently reported (RDx) mitigates HTN, and prevents renal inflammation in the deoxycorticosterone acetate (DOCA)-salt rat model of HTN. Although these findings suggest renal nerves directly mediate renal inflammatory signaling, this effect may also be secondary to lowering arterial pressure (AP). In this study, we aimed to elucidate the specific role of renal nerves on renal inflammatory signaling using a unilateral RDx approach to control for lowered AP. We tested the hypothesis that RDx will ameliorate the renal inflammation independent of HTN in the DOCA-salt rat. To test this hypothesis, 8 male Sprague Dawley (SD) rats were implanted with radiotelemeters to measure AP and subjected to unilateral RDx. Rats were then administered DOCA (100mg, s.c.) and 0.9% saline for 21 days. Rats were then anesthetized, and renal tissue and urine were collected from both RDx and contralateral control (CON) kidneys. Renal inflammation was assessed by assay for pro-inflammatory cytokines (IL-1β, IL-2, IL-6, GRO/KC, MCP-1) in both urine and renal tissue. Data presented as mean ± SEM, *p<0.05. Mean AP increased from 99±3 to 135±4mmHg over DOCA-salt treatment. Renal GRO/KC content was markedly reduced in RDx kidneys compared to CON (14±5* vs. 467±96pg/mg total protein), and this was mirrored in the urinary excretion of GRO/KC in RDx vs. CON (51±11* vs. 3717±500pg/mg creatinine). Similarly, renal MCP-1 content was lower in RDx (13±2*) compared to CON (292±51). Urinary excretion of MCP-1 was also decreased by RDx (67±31* vs. 1758±721). Finally, urinary protein:creatinine was abated by RDx (13±3* vs. 19±3au). Notably, there was no effect of RDx on renal or urinary content of IL-1β, IL-2, nor IL-6. From this data, we conclude that renal nerves mediate renal inflammation associated with chemokines GRO/KC and MCP-1 release, independent of HTN. However, RDx had no effect on IL-1β, IL-2, IL-6, which suggests a chemokine specificity of renal nerve contribution to inflammatory signaling. Studies are currently underway to establish the effect of RDx on renal infiltration of specific immune cell populations.