Role of the Renal Nerves in Renal Damage and Immune Cell Infiltration in Dahl Salt‐ Sensitive Rats

The present studies were performed to assess the role of the renal nerves in the development of renal damage and hypertension in Dahl Salt‐Sensitive (SS) rats. Initial experiments were performed in SS rats which underwent bilateral Renal sympathetic Denervation (RDN) or bilateral sham operation (n=8–10 per group). After 1 week, the rats were instrumented with radio‐telemeters for continuous measurement of blood pressure, and overnight urine collections were performed at baseline and the weekly for the duration of the study. Bilateral RDN did not alter baseline Mean Arterial Pressure (MAP) when the rats were fed a low salt (0.4% NaCl) diet (119±4 mmHg vs 122±2 mmHg in sham rats) or after 3 weeks of high salt (4% NaCl) diet (142±6 mmHg vs 147±5 mmHg in sham rats). Interestingly, the rats that underwent bilateral RDN demonstrated a significantly lower albumin excretion rate (70±5 mg/day) when compared to sham (149±10 mg/day). RDN was confirmed by demonstrating a significant reduction in tissue catecholamine concentration in the kidneys of RDN compared to sham rats (37±5 ng/g vs. 122±6 ng/g). We have previously demonstrated the critical role of infiltrating immune cells in the kidney in the development of hypertension and renal disease in SS rats. Therefore, we subsequently performed experiments to test the hypothesis that renal nerves contribute to renal damage in Dahl salt‐sensitive hypertension by increasing renal immune cell infiltration. To test this we used a unique model of unilateral RDN and contralateral sham to eliminate differences in circulating factors or systemic blood pressure and isolate the direct effects of renal nerves on the kidneys. Unilateral RDN and contralateral sham operation was performed and the rats were allowed to recover for 1 week. The diet was then switched from low to high salt and maintained for 3 weeks. Animals were euthanized and kidneys were collected for assessment of histologic renal damage using trichrome stained sections and evaluation of immune cell infiltration by flow cytometry. We observed no difference in total leukocyte (CD45+) infiltration between denervated and sham kidney (6.45±0.77 vs. 6.13±1.07 × 10 6 cells/kidney). There was also no difference in the numbers of CD3+ T cells, CD45R+ B cells or CD11b/c+ monocytes and macrophages. There were also no significant differences between RDN and sham kidneys histologically: glomerular damage was scored on the basis of glomerulosclerosis and mesangial expansion from 0(best) to 4(worst) (average glomerular score 2.2±0.2 vs 2.1±0.1) and tubular cast area indicative of tubular damage in outer medulla (12.6±1.0% vs 10.5±0.9%). Though our initial results suggested that renal nerves play a role in amplifying renal damage in SS hypertension independent of significant changes in blood pressure, subsequent studies suggest that this effect is not mediated by changes in renal immune cell infiltration. The results of this work suggest that immune cell infiltration in the kidney of SS rats is not mediated by renal nerves. Supported by DK96859 and HL116264. Support or Funding Information Supported by DK96859 and HL116264. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .