Abstract 325: Animal Models of Salt-Sensitive Hypertension Show Impaired Renal Sodium Chloride Cotransporter (NCC) Function

Abstract

Aim: These studies test the hypothesis that norepinephrine (NE) impairs renal NCC regulation to evoke salt-sensitive hypertension in Sprague-Dawley (SD) and Dahl Salt-Sensitive (DSS) rats. Methods: SD rats receiving a s.c. saline vehicle or NE (600ng/min) infusion were fed a 0.4% (NS) or high 8% NaCl (HS) diet for 14 days. Naïve DSS rats were placed on a NS or HS diet for 21 days. On day 14 or 21, MAP and peak natriuresis to i.v. hydrochlorothiazide (HCTZ; 2mg/kg) infusion was assessed. Plasma NE was measured and NCC immunoblotting was performed on kidney cortex tissue (N=5/6). Results: Excess NE significantly increased MAP and plasma NE levels in NE infused SD rats. A HS diet further increased plasma NE levels and MAP in both NE infused SD and DSS rats. HS intake failed to suppress NCC activity in NE infused SD rats and naïve DSS rats. Impaired NCC expression was shown in NE and HS treated SD rats. Conclusion: These findings reveal that NE infusion combined with a high salt diet in a salt-resistant phenotype evokes the physiological responses found in a genetic model of salt-sensitive hypertension. These data from both animal models support a direct role of NE on NCC function and the pathophysiology of salt-sensitivity.