Recent studies have implicated a role of
norepinephrine (NE) in the activation of the
sodium chloride cotransporter (NCC) to drive the development of
salt-sensitive
hypertension. However, the interaction between NE and increased
salt intake on blood pressure remains to be fully elucidated. This study examined the impact of a continuous NE infusion on
sodium homeostasis and blood pressure in conscious Sprague-Dawley rats challenged with a normal (NS; 0.6% NaCl) or high-
salt (HS; 8% NaCl) diet for 14 days. Naïve and saline-infused Sprague-Dawley rats remained normotensive when placed on HS and exhibited
dietary sodium-evoked suppression of peak natriuresis to
hydrochlorothiazide. NE infusion resulted in the development of
hypertension, which was exacerbated by HS, demonstrating the development of the
salt sensitivity of blood pressure [MAP (mmHg) NE+NS: 151 ± 3 vs. NE+HS: 172 ± 4; P < 0.05]. In these
salt-sensitive animals, increased NE prevented
dietary sodium-evoked suppression of peak natriuresis to
hydrochlorothiazide, suggesting impaired NCC activity contributes to the development of
salt sensitivity [peak natriuresis to
hydrochlorothiazide (μeq/min) Naïve+NS: 9.4 ± 0.2 vs. Naïve+HS: 7 ± 0.1; P < 0.05; NE+NS: 11.1 ± 1.1; NE+HS: 10.8 ± 0.4). NE infusion did not alter NCC expression in animals maintained on NS; however,
dietary sodium-evoked suppression of NCC expression was prevented in animals challenged with NE. Chronic NCC antagonism abolished the
salt-sensitive component of NE-mediated
hypertension, while chronic ANG II type 1 receptor antagonism significantly attenuated NE-evoked
hypertension without restoring NCC function. These data demonstrate that increased levels of NE prevent
dietary sodium-evoked suppression of the NCC, via an ANG II-independent mechanism, to stimulate the development of
salt-sensitive
hypertension.