Abstract 15295: Cardiac Sympathetic Afferent Stimulation Increases Brain ENaCs, thereby Concomitant Salt Loading Leads to Sympathoexcitation
Background: Recently, we demonstrated in mice with pressure overload, brain epithelial Na channels (ENaCs) increased and concomitant salt loading induced sympathoexcitation (Circ Res 2010). However, how diseased heart, such as chronic pressure overload increased brain ENaCs remains unknown. We hypothesized cardiac sympathetic afferent (CSA) stimulation increases brain ENaCs resulting in salt-induced sympathoexcitation.
Methods and Results: Adult male Institute Cancer Research mice were used in the present study. We stimulated CSA by epicardial application of a piece of filter paper (2×2mm) containing capsaicin (15μ g/μ L in 2μ L, CAP) or ethanol (CNT). 3 days after the operation, in comparison with CNT, CAP upregulated αENaCs in the brain (circumventricular tissues including hypothalamus) [αENaCs/GAPDH; 1.12+0.08 vs. 0.51+0.10, p<0.05]. The expressions of other subunits of ENaCs (βENaCs and γENaCs) did not differ between the groups. To examine the impact of salt loading on sympathoexcitation, we fed mice with a high-salt diet (8%) (HS) or a regular salt diet (RS) for 5 days. In comparison with RS, HS increased urinary norepinephrine excretion (uNE, a marker of sympathetic activity) in CAP [uNE: 992±60 vs. 538±30 ng/day, n=6 for each, p<0.05], but not in CNT indicating CSA induced upregulation of αENaCs is prerequisite for salt sensitive sympathoexcitation. We further examined the impact of natural CSA stimulation by ischemia (coronary ligation, MI) or pressure load (suprarenal abdominal aortic banding, AB) for 4 weeks on sympathoexcitation. In comparison with Sham operation, both MI and AB upregulated brain αENaC [αENaCs/GAPDH; MI: 1.21+0.11 vs. 0.51+0.09, p<0.05 AB: 0.81+0.09 vs. 0.46+0.09, p<0.05]. MI increased uNE before salt loading compared with sham operated mice [714±30 vs 422±15 ng/day, n=8 for each, p<0.05]. HS increased uNE both in MI and AB [MI: 1113±64 (n=6) vs. 714±30 (n=8) ng/day, p<0.05, AB: 785+74 vs. 262+32 ng/day, n=6 for each, p<0.05], while RS did not change in either mice or sham operated mice.
Conclusion: CSA stimulation upregulates brain ENaCs, thereby concomitant salt loading leads to sympathoexcitation.
- © 2012 by American Heart Association, Inc.