LBOS 02-01 HYPERTENSION, ALDOSTERONE AND EPC-MEDIATED ENDOTHALIAL INJURY REPAIR.

OBJECTIVE: Hyperaldosteronemia exerts adverse effects on vascular endothelium except enhanceing blood pressure; however, the impacts and molecular mechanisms of hyperaldosteronemia on endothelial progenitor cell (EPC)-mediated endothelial repair are yet to be determined. The aim of this study was to investigate the endothelial repair capacity of EPCs from hypertensive patients with primary hyperaldosteronemia (PHA).

DESIGN AND METHOD: In vivo endothelial repair capacity of EPCs from PHAs (n = 20), age- and blood pressure-matched essential hypertension patients (n = 20), and age-matched healthy subjects (n = 20) was evaluated by transplantation into nude mice with carotid artery denudation injury. Endothelial function was evaluated by flow-mediated dilation of brachial artery in human subjects.

RESULTS: In vivo endothelial repair capacity of EPCs and flow-mediated dilation were impaired both in PHAs and in essential hypertension patients; however, the EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs were declined more seriously than essential hypertension patients. Oral spironolactone improved EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs. Increased oxidative stress, oxidative 5,6,7,8-tetrahydrobiopterin degradation, endothelial nitric oxide synthase uncoupling and decreased nitric oxide production were found in EPCs from PHAs. Nicotinamide adenine dinucleotide phosphate oxidase subunit p47(phox) knockdown or 5,6,7,8-tetrahydrobiopterin supplementation attenuated endothelial nitric oxide synthase uncoupling and enhanced in vivo endothelial repair capacity of EPCs from PHAs.

CONCLUSIONS: The present study demonstrated PHAs exhibited more impaired endothelial repair capacity of EPCs than did essential hypertension patients independent of blood pressure, which was related with mineralocorticoid receptor-dependent oxidative stress and subsequently 5,6,7,8-tetrahydrobiopterin degradation and endothelial nitric oxide synthase uncoupling.