P9.06 EVIDENCE FOR A ROLE OF THE VASCULAR ENDOTHELIUM IN THE REGULATION OF ARTERIAL WALL VISCOSITY IN VIVO IN HUMANS

Abstract

Although the viscoelasticity of large arteries has been extensively investigated, few studies have focused on arterial wall viscosity (AWV) itself and its regulation by the endothelium in vivo. This is of particular importance since AWV is a major source of energy dissipation through the vascular system reducing cardiovascular coupling efficiency. We simultaneously measured radial artery diameter and arterial pressure (NIUS02) in healthy volunteers before and after local infusion of L-NMMA (8μmol/min) as NO-synthase inhibitor, tetraethylammonium (TEA: 9μmol/min), as blocker of calcium-activated potassium channels, the target of endothelium-derived hyperpolarizing factors (EDHF), fluconazole (0.4mmol/min), as inhibitor of EDHF synthesis by cytochrome epoxygenases and L-NMMA associated with TEA or with fluconazole. AWV was estimated from the ratio of the area of the hysteresis loop of the pressure-diameter relationship to the area representing the whole energy exchanged during each cardiac cycle. L-NMMA paradoxically reduced AWV (n=5: 27.6±0.7 to 23.4±0.7%, P=0.053). Conversely, AWV was increased by TEA (n=6: 25.5±0.5 to 31.3±0.7%, P=0.040) and fluconazole (n=5: 26.6±0.6 to 30.6±0.6%, P=0.047). This increase was more marked with the association of L-NMMA+TEA (n=6: 27.6±0.9 to 41.0±0.7%, P=0.002) and L-NMMA+fluconazole (n=6: 26.1±0.7 to 36.3±0.3%, P=0.001) showing a synergistic effect of both combinations on AWV. These results demonstrate that the endothelium contributes in vivo in humans to the regulation of AWV through an interaction between NO and cytochrome-related EDHF release. Therefore, the prevention of endothelial dysfunction appears a critical target to improve cardiovascular coupling and thus may help to limit the development of complications in cardiovascular diseases.