Abstract 053: Increased Arterial Pressure Precedes Renal Dysfunction And Elevated Renal Sympathetic And Afferent Nerve Activity In Deoxycorticosterone-Salt Rat

Abstract

Hypertension (HTN) is a primary risk factor for cardiovascular disease - the leading cause of death worldwide. HTN is multifaceted but a key factor is aberrant autonomic signaling, including renal sympathetic (RSNA) and afferent nerve activity (ARNA). ARNA is elevated in several models of HTN and renal afferent nerve ablation can mitigate the HTN. It is unknown if ARNA rises before changes in blood pressure (BP) or renal function in HTN. This study aimed to determine when renal nerve activity changes vis a vis BP and renal function in a model of salt sensitive HTN. We hypothesized increased ARNA and RSNA would coincide with a rise in BP and decline in renal function. To test this hypothesis, 24 uninephrectomized male Sprague Dawley rats (300g) received a deoxycorticosterone acetate (DOCA; 100mg, SC) implant and 0.9% NaCl drinking water. Renal function (serum creatinine; Cr) and systolic BP (SBP; tail cuff) were measured weekly. Animals were randomly allocated to acute renal nerve recording on protocol day (D) 0, 7, 14, or 21. Multiunit RSNA and ARNA were recorded serially, as ARNA was isolated after sectioning proximal side. RSNA is expressed as bursts/heartbeat, ARNA and expressed as %ARNA max (response to intrapelvic capsaicin). Data were analyzed by one-way ANOVA with Bonferroni post hoc. Data presented as mean±SEM; *p<.05 vs D0. SBP (mmHg) progressively increased on D7 (*152 ± 3), D14 (*171 ± 3), and D21 (*197 ± 7) vs D0 (138 ± 3). ARNA (%) increased at D14 (*23.0 ± 4.7) and D21 (*34.2 ± 4.4) vs D0 (10.1 ± 0.8), but no changes were detected at D7 (13.4 ± 2.1). No changes in RSNA from D0 were detected. Cr (mg/dL) increased at D14 (*1.2 ± 0.1) and D21 (*1.2 ± 0.1) vs D0 (0.9 ± 0.0), indicating a decline in kidney function. These data do not support the hypothesis that ARNA and RSNA increase in parallel to increasing BP. Rather, BP appears to initially increase independent of detectable changes in RSNA, ARNA or renal dysfunction. Interestingly, renal dysfunction and elevated ARNA were detected on D14, which coincides with our previous report that renal inflammation is first detected at D14. These data do not support a causal role of ARNA in this model. Rather, ARNA may subsequently drive disease progression. Further studies on the cause of increased ARNA and inflammation interaction are underway.