Abstract 2996: Captopril Restores Endothelial Dysfunction Induced by Acute Salt Loading and Angiotensin II Infusion in Healthy Salt-Sensitive African American Men
The etiology of salt-sensitive hypertension in African-Americans (AA) is poorly understood. Previous animal model and human studies have suggested an association between acute salt (Na) loading, transient impairment of endothelial function, increased oxidative stress and the activation of vascular and renal angiotensin (AngII) systems. This study tests the hypothesis that AngII system blockade with Captopril will reduce AngII-dependent oxidative stress and reverse endothelial dysfunction in salt-sensitive AA. Our study included 16 healthy, non-hypertensive AA men (25 ± 6 yrs, range 18 – 41) under carefully controlled conditions while on high sodium balance diet (200meq/d for 5 days). We assessed the renal blood flow (RBF) response (PAH clearance) to exogenous AngII or Captopril, as an indirect measure of intrarenal angiotensin system activity. To determine salt sensitivity of blood pressure (BP), all subjects additionally received isotonic 0.9% saline infusion (500 ml/hr for 4hrs) followed by oral Lasix and were divided into 2 groups (salt sensitive, SS and salt resistant, SR) based on their systolic BP response (SS= > 10% difference). As expected, 5/16 subjects (31%) were SS (change from 112 ± 3 to 129 ± 4 mmHg, p < .001) and the remainder SR (change from 112 ± 4 to 114 ± 4 mmHg, p = ns). The SS group exhibited a significant decrease in brachial artery endothelium-dependent flow-mediated dilation (FMD, measured by ultrasound) in response to Na loading vs the SR group (10% vs. 2%, p < .01). This endothelial dysfunction was associated with increased oxidative stress as assessed by the ratio of reduced/oxidized glutathione (35% vs. 1%, p < .01). The infusion of AngII (3ng/kg/min iv for 45 min) induced a profound, 2-fold decrease in RBF in the SS subjects vs the SR group (p < .05). Conversely, both groups showed a two-to three-fold increase in both RBF and FMD after acute Captopril treatment (p < .05). In summary, our study is among the first to show that acute sodium loading promotes oxidative stress and a transient impairment in endothelial function that can be reversed by acute Captopril treatment in healthy SS AA subjects. These results have implications for elucidating the role of AngII in the pathogenesis of salt-sensitive hypertension in AA.