Abstract 12073: Role of Epoxyeicosatrienoic Acids in the Conduit Artery Endothelial Dysfunction Associated with Essential Hypertension
Background. The mechanisms involved in the endothelial dysfunction of conduit arteries, which is an independent contributor to the high incidence of cardiovascular events during essential hypertension, remain to be fully elucidated.
Methods and results. Radial artery diameter, blood flow and mean wall shear stress were determined in 28 non-treated essential hypertensive patients and 30 normotensive control subjects, during endothelium-dependent flow-mediated dilatation (FMD) induced by hand skin heating. The role of epoxyeicosatrienoic acids (EETs) and NO was assessed during heating using the brachial infusion of inhibitors of cytochrome P450 epoxygenases (fluconazole) and NO-synthase (L-NMMA). First, as compared with controls, hypertensive patients exhibited a decreased FMD in response to post-ischemic hyperemia as well as to heating (mean±SD: 0.484±0.104 vs. 0.373±0.132 mm) , as confirmed by the lesser slope of their diameter-shear stress relationship, with no modification in endothelium-independent dilatation. In controls, heating-induced FMD was reduced by fluconazole (-0.126±0.029 mm), L-NMMA (-0.237±0.027 mm) and, to a larger extent, by L-NMMA+fluconazole (-0.352±0.037 mm). In patients, FMD was not affected by fluconazole (-0.034±0.027 mm) and was reduced by L-NMMA (-0.162±0.028 mm) and L-NMMA+fluconazole (-0.188±0.029 mm) to a lesser extent than in controls. Local plasma EETs level increased during heating in controls (12.8±4.5 to 17.9±4.4 ng/mL) but not in patients (13.9±4.0 to 15.1±5.8 ng/mL).The increase in plasma EETs in controls was reduced by fluconazole. Plasma nitrite level, an indicator of NO availability, increased during heating in controls (176±30 to 229±34 nmol/L) and to a lesser extent in patients (140±66 to 163±64 nmol/L). The increase in plasma nitrite was abolished by L-NMMA in both groups. Plasma endothelin-1 level decreased during heating in controls (2.49±0.82 to 1.91±0.83 pmol/L) but not in patients (3.18±0.99 to 3.24±0.72 pmol/L).
Conclusions. These results show that an impaired role of EETs contributes together with alterations in NO and endothelin-1 pathways to conduit artery endothelial dysfunction in essential hypertension.
- © 2011 by American Heart Association, Inc.