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, remains 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, as shown 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, L-NMMA and, to a larger extent, by L-NMMA+fluconazole. In patients, FMD was not affected by fluconazole and was reduced by L-NMMA and L-NMMA+fluconazole to a lesser extent than in controls. Local plasma EETs level increased during heating in controls (an effect diminished by fluconazole), but not in patients. Plasma nitrite level, an indicator of NO availability, increased during heating in controls (an effect abolished by L-NMMA), and to a lesser extent in patients. Plasma endothelin-1 level decreased during heating in controls but not in patients.

Conclusions. These results show that an impaired role of EETs contributes with alteration in NO and endothelin-1 pathways to conduit artery endothelial dysfunction in essential hypertension.