Renal denervation (RDN) may be an effective treatment for hypertension; however, the mechanisms remain unknown. RDN mitigates hypertension in addition to the concomitant renal inflammation in the deoxycorticosterone (DOCA)-salt rat model. Renal inflammation is hypothesized to drive the hypertension, but the timing and relationship to mean arterial pressure (MAP) remain elusive. We aimed to elucidate the temporal inflammatory and MAP response to DOCA-salt through urinary cytokine excretion, and test its responsiveness to renal denervation. We hypothesized that (a) RDN would mitigate renal and urinary cytokine content, and (b) a decrease urinary cytokine would precede changes in MAP.
12 uninephrectomized male Sprague Dawley rats (300–325 g) received either surgical renal denervation (RDN; n = 6) or sham (Sham; n = 6). One week following, rats were administered DOCA (100 mg) and 0.9% saline for 21 days. Urine samples were collected weekly. Urinary and renal tissue cytokines (IL-1β, IL-2, IL-6, GRO/KC, MCP-1) were measured by multiplex assay. Temporal data analyzed by two-way ANOVA with Bonferroni post-hoc test (α=0.05). All other data were analyzed by Student's t-test. Data presented as mean ± SEM.
MAP response to DOCA-salt was attenuated (*p < .05) by RDN vs. Sham, where MAP significantly diverged at Days 14–21 (see Table). Similarly, all measured renal cytokines were markedly reduced (*p < .05) in RDN vs. Sham - a reduction of 42–70% of Sham values (see Table). Urinary cytokine excretion on day 21 mirrored this effect, where each cytokine was lower (*p < .05) in RDN vs. Sham – reduced by 44–84% Sham values (see Table). No difference was detected between RDN and Sham urinary cytokine content on Days 0–7, and only urinary IL-1β and IL-2 were reduced (*p < .05) at Day 14.
In conclusion, these data support our hypothesis that urinary cytokines reflect renal inflammatory cytokine content, and both are abated by RDN. However, our second hypothesis was not supported, as differences in MAP appeared prior to a significant reduction of most urinary cytokines. With these findings, we hypothesize that hypertension may precede renal inflammation in this model. Further studies are necessary to elucidate the driving force for renal inflammation in this model.
University of Minnesota, Minneapolis, MN, USA