Abstract 121: Afferent Renal Nerve Chemo- and Mechanosensitive Responses and the Modulation of Sodium Homeostasis and Blood Pressure

Abstract

Aim: We hypothesize that challenges to sodium homeostasis differentially activate chemo- vs. mechanosensitive afferent renal nerves to evoke sympathoinhibition, sodium homeostasis and normotension in the Sprague-Dawley (SD) rat. Methods: Conscious SD rats, post sham (S) or afferent renal nerve ablation (Renal-CAP; capsaicin 33 mM) underwent IV volume expansion (VE; 5% BW) or IV sodium loading (1M NaCl Infusion – constant infusion volume) and HR, MAP, natriuresis and PVN neuronal activation (c-Fos expression) were assessed (N=4/gp). Naïve SD rats were fed a 0.6% (NS) or 4% NaCl (HS) diet for 21 days and afferent renal nerve activity was assessed as norepinephrine (NE) (1250 pmol) and NaCl-evoked (450mM) substance P (SP) release in a renal pelvic assay (N=4/gp). Radiotelemetered SD rats post S or Renal-CAP immediately prior a 0.6% (NS) or 4% NaCl (HS) diet underwent continuous MAP monitoring. On day-21 plasma and renal NE content was assessed (N=5/group). Results: Renal-CAP attenuated the natriuretic and PVN parvocellular responses to IV VE (peak UNaV [μeq/min]; S 43±4 vs Renal-CAP 26±6, P<0.05, PVN Medial Parvocellular neuronal activation [c-fos positive cells]; S 49±6 vs Renal-CAP 22±5 P<0.05) and evoked increased MAP (MAP 90min post-VE [mmHg] S 118±3 vs Renal-CAP 132±4, P<0.05). In contrast Renal-CAP did not alter the natriuresis to IV 1M NaCl (UNaV [μeq/min]; S 21±4 vs Renal-CAP 21±3) or increase MAP. In naïve SD rats HS-intake did not alter MAP and suppressed plasma and renal NE (P<0.05). HS intake increased NE, but not NaCl, mediated afferent renal nerve activity (NE-evoked peak ΔSP [ng/ml); NS 14±2, HS 22±3, P<0.05, NaCl-evoked peak ΔSP [ng/ml]; NS 17±3, HS 16±2). Renal-CAP immediately prior to a HS-intake persistently increased MAP (Day 21 MAP [mmHg] S HS 106±4, Renal-CAP HS 123±5, P<0.05) and attenuated HS-evoked global and renal sympathoinhibition (P<0.05). Conclusion: The mechanosensitive afferent renal nerves mediate acute natriuresis and blood pressure regulation via activation of PVN sympathoinhibitory neurons. During HS intake the afferent renal nerves counter the development of salt-sensitive hypertension via a mechanism involving increased mechano but not chemosensitive afferent nerve responsiveness to potentiate sympathoinhibition.