Abstract P1114: Impairment of Nitric Oxide Induces Volume Expansion in Normotensive Salt-Sensitivities by Activating NCC

Abstract

Background: It is still controversial if salt-sensitivity in terms of regulation of circulating volume in normotensive. In the present study, we investigated the role of NO on salt-sensitivity by measuring salt-induced increases in circulating volume and its underlining mechanisms. Method: We measured circulating volume, change in blood pressure and renal sodium-chloride cotransporter (NCC) activation, both in vivo in SD rats, wild-type mice and NCC deficient mice, and in vitro in mDCT cells. Result: The blood volume was comparable between the groups during NS diet period, and increased a day after HS loading. The blood volume returned to the level of NS period in HS group, in contrast, continuously increased in L-NAME + HS group (Fig A). Corresponding to the increases in blood volume, HS+L-NAME group increased blood pressure (Fig B) (MBP: HS: 105.7 ± 4.1 vs. HSL: 111.5 ± 3.5 mmHg). This blood pressure response to high salt diet was reproduced in C57BL/6J mice after 4 weeks treatment (HS: 108.7 ± 3.7 vs. HSL: 130.5 ± 2.9 mmHg). There is no kidney morphological changes. In vivo experiments showed that HCTZ but no amiloride induced larger natriuretic effect in L-NAME+HS group, which suggest NCC rather than ENaC is responsible. The phosphorylated NCC is reduced after HS but it sustained in L-NAME+HS group. Moreover, the results from NCC-deficient mice support that NCC is indispensable for L-NAME induced salt sensitivity. In addition, the membrane NCC expression was decreased by NO in a time and dose depended manner in mDCT cells. Conclusion: Low dose L-NAME induces volume expansion leading to salt-sensitivity by inappropriately and directly activate NCC in both vivo and vitro.