Abstract P202: Impaired Central, Renal, and Blood Pressure Responses to Alterations in Fluid and Electrolyte Homeostasis in Aged Sprague-Dawley Rats

Abstract

Aim: Hypertension is strongly correlated with increased age in human subjects. These studies tested the hypothesis that impaired natriuretic responses to acute and chronic challenges to fluid and electrolyte homeostasis contribute to age-dependent hypertension. Methods: Two-month old (young) and 6-month old (aged) male Sprague-Dawley rats underwent an acute IV volume expansion (VE; 5% BW) and MAP, HR, urine output, and PVN neuronal activation (c-Fos expression) were assessed (n=4 per group). In a separate study, naïve 2 and 6-month old male Sprague-Dawley rats were maintained on a normal (0.6% NaCl) or high salt (4% NaCl) diet, and on day 21, MAP and NCC activity (peak natriuresis to IV HCTZ, 2mg/kg) were assessed (n=4 per group). Results: Renal excretion of sodium and water after acute VE was impaired in aged rats (total % sodium load excreted; young 78±6 vs aged 60±7: total % water load excreted; young 96±7 vs aged 66±5, P<0.05). PVN neuronal activation was attenuated in response to acute VE in aged rats in all parvocellular regions excluding the lateral parvocellular subnucleus (PVN neuronal activation [c-fos positive cells]; medial parvocellular young 59±4 vs aged 42±7, P<0.05). CV parameters did not change in response to acute VE in either group. Chronic HS diet evoked an increase in MAP in aged rats but not young rats (MAP [mmHg]; young NS 124±2 vs young HS 126±3 vs aged HS 138±3, P<0.05). Chronic HS diet caused a decrease in NCC activity in young rats and, in contrast, an increase in aged rats (peak ΔUNaV to HCTZ [μeq/min]; young NS 9.2±0.5 vs young HS 7.1±0.3 vs aged HS 16±1, P<0.05). Conclusion: Activation of sympathoinhibitory PVN parvocellular neurons is a well-characterized response to acute VE. Our data suggest there are attenuated acute PVN sympathoinhibitory responses to alterations in fluid and electrolyte balance in aged rats. In aged animals, HS intake increased NCC-mediated sodium reabsorption and promoted the development of sodium-dependent hypertension. We speculate that this is driven by blunted HS-evoked sympathoinhibition, likely due to reduced PVN neuronal activation.