Abstract 197: Effect of Selective Afferent Renal Denervation by Periaxonal Application of Capsaicin on Salt Sensitivity of Arterial Pressure

Abstract

Renal nerves contribute to some forms of hypertension, but the differential role of afferent and efferent renal nerves remains unclear. It has been proposed that afferent renal nerves modulate arterial pressure (AP) since rats subjected to dorsal rhizotomy (DRX) at spinal levels T9-L1 exhibit salt-sensitive hypertension. Since DRX is not selective for renal afferents, we developed a novel method for selective ablation of calcitonin gene-related peptide (CGRP) positive sensory fibers in the kidney and tested the hypothesis that, as with DRX, our method of afferent renal denervation (ARDN) causes salt-dependent hypertension in rats. Male Sprague Dawley rats were implanted with radiotelemeters to measure AP and heart rate (HR) and underwent either ARDN (renal-CAP) or sham surgery (SHAM). In renal-CAP rats, the renal nerves were exposed to a 33 mM capsaicin solution for 15 minutes. The rats were housed in metabolic cages, fed a 0.1% NaCl diet and allowed to recover for 10 days. After a 4 day baseline period, the diet was increased to 4% NaCl for 3 weeks then 8% NaCl for 2 weeks. At the end of the protocol the rats were euthanized and immunohistochemistry (IHC) was performed on the kidneys labeling for CGRP, as a marker of afferent renal fibers, and tyrosine hydroxylase, as a marker of efferent renal fibers. Baseline mean AP (mmHg) was slightly higher in renal-CAP (103 ± 2) than SHAM rats (97 ± 3) whereas HR (BPM) was similar (399 ± 11 vs. 395 ± 10). Increasing salt intake caused a similar increase in MAP in both groups, but HR decreased more in SHAM than renal-CAP rats (358 ± 6 vs. 385 ± 3 BPM). Sodium and water intake, excretion and balance were not different between the two groups. IHC confirmed the selective destruction of renal afferent fibers. These data suggest that: 1) renal-CAP treatment is an effective method for ARDN, 2) afferent renal nerves play a minimal role in the regulation of AP or sodium and water balance in normotensive rats, regardless of salt intake and 3) afferent renal nerves appear to mediate sodium dependent decreases in HR. The discrepancy between these results and those of previous studies may be due to the non-selective nature of DRX.