Abstract 085: The Role of Afferent and Efferent Renal Nerves in T Lymphocyte Recruitment into the Kidneys and Development of Two Models of Salt-Dependent Hypertension

Abstract

Renal denervation (RDNX) attenuates hypertension (HT) in some animal models and human patients, yet the antihypertensive mechanisms involved are not known. Because it has been suggested that efferent renal nerves may cause recruitment of T lymphocytes (T cells) into the kidneys, and T cell-secreted cytokines can activate afferent neurons, we hypothesized that RDNX attenuates HT in the angiotensin II (AngII)-salt and deoxycorticosterone acetate (DOCA)-salt models by decreasing efferent renal nerve-dependent T cell trafficking to the kidneys and T cell-mediated activation of afferent renal nerves. Male Sprague-Dawley rats underwent SHAM surgery, RDNX or selective ablation of afferent renal nerves (renal-CAP) and were subjected to either AngII-salt or DOCA-salt HT. AngII-salt rats underwent SHAM, RDNX or renal-CAP (n = 8/group) and were instrumented with an IV catheter and radio-telemeter to measure mean arterial pressure (MAP). Rats were fed a 4% NaCl diet and, after a baseline period, AngII was infused IV (10 ng/kg/min) for 16 days. DOCA-salt rats were unilaterally nephrectomized and, after 2 weeks, instrumented with a radio-telemeter, subjected to SHAM (n = 5), RDNX (n = 7) or renal-CAP (n = 6) and given 0.9% saline to drink. After a baseline period, silicone pellets containing 100mg DOCA were implanted SC and rats were sacrificed 3 weeks later. Upon sacrifice, kidneys were harvested for flow cytometry to determine the number of CD4+ and CD8+ T cells in the kidneys. In AngII-salt rats, renal CD4 and CD8 T cell counts and the change in MAP from baseline (ΔMAP) were similar between groups (SHAM = 42.3 ± 6.4 mmHg, RDNX = 32.6 ± 5.9 mmHg, renal-CAP = 36.8 ± 5.0 mmHg). In DOCA-salt rats, RDNX and renal-CAP significantly attenuated ΔMAP (SHAM = 24.2 ± 3.1 mmHg, RDNX = 12.7 ± 2.4 mmHg, renal-CAP = 13.8 ± 1.7 mmHg). CD8 T cell counts in RDNX kidneys were significantly lower than SHAM (p < 0.01) and trended lower than renal-CAP. CD4 T cell counts in RDNX kidneys were significantly lower than renal-CAP (p < 0.05) and trended lower than SHAM. These data show that renal nerves do not contribute to AngII-salt HT, but suggest that afferent renal nerves contribute to DOCA-salt HT and that this may be T cell-mediated and dependent on efferent renal nerves. Funding: R01 HL116476-01.