Abstract 085: Renal and Neural Mechanisms of Age-Related Hypertension

Abstract

Aim: Hypertension (HTN) is positively correlated with age and sympathetic tone in humans. We hypothesize that sympathetically driven sodium chloride cotransporter (NCC)-mediated sodium retention contributes to age-related HTN. Methods: Three, 8 and 16 month old male SD rats on a normal salt (NS; 0.6% NaCl) diet underwent an acute IV volume expansion (VE; 5% body weight – mechanoreceptor stimulus) or 1M NaCl infusion (20μL/min, 2hr – chemoreceptor stimulus) and mean arterial pressure (MAP), natriuresis (UNaV) and paraventricular nucleus (PVN) neuronal activation (c-Fos expression) were assessed. In separate groups of rats fed a 21 day NS or high salt (HS; 4% NaCl) diet, 1) ex vivo afferent renal nerve (ARN) activity (norepinephrine-evoked substance P release) or 2) in vivo MAP, NCC activity (ΔUNaV to IV hydrochlorothiazide, 2mg/kg) and sympathetic tone were assessed. N=4-6/gp. Results: The natriuretic and PVN sympathoinhibitory parvocellular neuronal responses to VE, but not 1M NaCl infusion, are blunted in aged rats. Aged rats exhibit reduced ARN activity on a NS diet and fail to increase ARN activity on a HS diet. Aged rats develop salt sensitive HTN accompanied by elevated NCC activity and sympathetic tone on a NS diet and impaired suppression of NCC activity and sympathetic tone on a HS diet. Conclusion: Aging is associated with a selective impairment in the mechanosensitive ARN and salt sensitive HTN. We speculate that an age-related decrease in the mechanosensitive ARN sympathoinhibitory reno-renal reflex promotes sympathoexcitation, perhaps via reduced activity of PVN sympathoinhibitory parvocellular neurons, driving NCC-mediated sodium retention and salt sensitive HTN.