06.03 Nitric Oxide and Endothelium-Derived Hyperpolarizing Factor Regulate the Adaptation of Human Conduit Artery Mechanics to Changes in Shear Stress

Abstract

The role of NO and endothelium-derived hyperpolarizing factor (EDHF), synthesized by cytochrome epoxygenases and acting through calcium-activated potassium (KCa) channels, in the flow-mediated regulation of human conduit artery mechanics has never been investigated.

In 11 healthy volunteers, whole blood viscosity, arterial pressure, radial artery diameter, wall thickness and flow (echotracking) were measured during hand skin heating in the presence of saline and the NO-synthase inhibitor, L-NMMA, infused alone and combined with the inhibitors of KCa channels, tetraethylammonium, and cytochrome epoxygenases, fluconazole. Wall shear stress, the flow-dependent stimulus, was calculated (Poiseuillean model). Arterial compliance, elastic wall modulus were calculated and fitted as functions of midwall stress (wall loading conditions) to suppress the confounding influence of changes in geometry.

Heating induced in all cases an increase in radial artery flow, diameter, shear stress and midwall stress and a decrease in wall thickness without change in arterial pressure. The increase in diameter with shear stress was reduced by L-NMMA and, in a more extent, by both combinations. Heating induced an upward shift of the compliance-midwall stress curve and a downward shift of the modulus-midwall stress curve under saline demonstrating an associated decrease in smooth muscle tone and wall stiffness with the shear stress increase. The shifts of these curves were decreased by L-NMMA and abolished by both combinations.

These results demonstrate that NO and EDHF regulate the adaptation of conduit artery mechanics to shear stress variations in humans suggesting the major role of the endothelium in maintaining arterial conductance and adjusted cardiac load.