Abstract 664: Increased Endothelial Expression of NADPH Oxidase-p47phox in Human Hypertension
Introduction: Hypertensive patients have impaired endothelial-dependent vasodilation. Endothelial nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p47 subunit (p47phox) may contribute to hypertension (HTN) via generation of reactive oxygen species. NADPH oxidase derived superoxide has been shown to inactivate nitric oxide, a potent vasodilator produced by endothelial nitric oxide synthase (eNOS) in endothelial cells (EC), causing endothelial dysfunction. EC expression of p47phox and eNOS in human HTN has not been previously assessed.
Methods: We assessed endothelial function in 20 Stage 1 hypertensive subjects (mean age 50 years, 55% female) and 18 normotensive (NT) controls (mean age 47 years, 68% female) by brachial artery flow mediated dilation (FMD) and extracted venous EC by J-wires via forearm catheters. Expression of p47phox, eNOS, and phosphorylated eNOS at serine 1177 residue (peNOS) was captured by immunofluorescence microscopy using human umbilical vein endothelial cell (HUVEC) controls.
Results: FMD was lower in hypertensive compared to NT subjects (6.3±0.6 versus 8.5±1.0 %, p < 0.05). In EC, expression of eNOS and p47phox was greater in hypertensive compared to NT subjects (0.52±0.07 vs 0.32±0.03, p=0.02) and (0.38±0.03 vs 0.27±0.03, p=0.003), respectively, Figure 1. PeNOS was not different between groups. In EC, p47phox expression significantly correlated with blood pressure after adjustment for body mass index (r = 0.39, p = 0.02).
Conclusion: We found impaired endothelial function and enhanced EC expression of NADPH oxidase p47 subunit, the major oxidant enzyme responsible for vascular superoxide formation, in human hypertension.
Author Disclosures: E.B. Solow: B. Research Grant (includes principal investigator, collaborator, or consultant and pending grants as well as grants already received); Modest; American Heart Association Research Grant, Bristol Myers Squibb Research Grant. S.M. Danesh: None. E. Onwuegbuchu: None. A. Velasco: None. P. Raheja: None. D. Arbique: None. Z. Wang: None. A.L. Price: None. C. Mineo: None. W. Vongpatanasin: None.
- © 2014 by American Heart Association, Inc.